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  Subjects -> BIOLOGY (Total: 2601 journals)
    - BIOCHEMISTRY (192 journals)
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BIOCHEMISTRY (192 journals)                  1 2     

AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Acetic Acid Bacteria     Open Access   (Followers: 1)
ACS Chemical Biology     Full-text available via subscription   (Followers: 252)
ACS Chemical Neuroscience     Full-text available via subscription   (Followers: 13)
Acta Crystallographica Section D : Biological Crystallography     Hybrid Journal   (Followers: 8)
Acta Crystallographica Section F: Structural Biology Communications     Hybrid Journal   (Followers: 5)
Advances and Applications in Bioinformatics and Chemistry     Open Access   (Followers: 7)
Advances in Biological Chemistry     Open Access   (Followers: 5)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 6)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 6)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 10)
African Journal of Biochemistry Research     Open Access  
African Journal of Chemical Education     Open Access   (Followers: 1)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 4)
American Journal of Biochemistry     Open Access   (Followers: 6)
American Journal of Biochemistry and Biotechnology     Open Access   (Followers: 146)
American Journal of Biochemistry and Molecular Biology     Open Access   (Followers: 11)
Amino Acids     Hybrid Journal   (Followers: 7)
Analytical Biochemistry     Hybrid Journal   (Followers: 172)
Annals of Clinical Biochemistry     Hybrid Journal   (Followers: 1)
Annual Review of Biochemistry     Full-text available via subscription   (Followers: 28)
Annual Review of Chemical and Biomolecular Engineering     Full-text available via subscription   (Followers: 10)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 18)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 7)
Applied Organometallic Chemistry     Hybrid Journal   (Followers: 4)
Archives of Biochemistry and Biophysics     Hybrid Journal   (Followers: 9)
Archives of Insect Biochemistry and Physiology     Hybrid Journal   (Followers: 1)
Archives Of Physiology And Biochemistry     Hybrid Journal   (Followers: 1)
Asian Journal of Biochemistry     Open Access   (Followers: 1)
Bangladesh Journal of Medical Biochemistry     Open Access   (Followers: 2)
BBA Clinical     Open Access  
BBR : Biochemistry and Biotechnology Reports     Open Access   (Followers: 4)
Biochemical and Biophysical Research Communications     Hybrid Journal   (Followers: 13)
Biochemical and Molecular Medicine     Full-text available via subscription   (Followers: 2)
Biochemical Engineering Journal     Hybrid Journal   (Followers: 8)
Biochemical Genetics     Hybrid Journal   (Followers: 2)
Biochemical Journal     Full-text available via subscription   (Followers: 15)
Biochemical Pharmacology     Hybrid Journal   (Followers: 6)
Biochemical Society Transactions     Full-text available via subscription   (Followers: 2)
Biochemical Systematics and Ecology     Hybrid Journal   (Followers: 3)
Biochemistry     Full-text available via subscription   (Followers: 178)
Biochemistry (Moscow)     Hybrid Journal   (Followers: 3)
Biochemistry (Moscow) Supplement Series A: Membrane and Cell Biology     Hybrid Journal   (Followers: 4)
Biochemistry (Moscow) Supplemental Series B: Biomedical Chemistry     Hybrid Journal   (Followers: 4)
Biochemistry and Cell Biology     Full-text available via subscription   (Followers: 9)
Biochemistry and Molecular Biology Education     Hybrid Journal   (Followers: 3)
Biochemistry and Molecular Biology of Fishes     Full-text available via subscription   (Followers: 1)
Biochemistry Research International     Open Access   (Followers: 4)
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids     Hybrid Journal   (Followers: 3)
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease     Hybrid Journal   (Followers: 17)
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research     Hybrid Journal   (Followers: 5)
Biochimie     Hybrid Journal   (Followers: 4)
Bioconjugate Chemistry     Full-text available via subscription   (Followers: 14)
BioDrugs     Full-text available via subscription   (Followers: 7)
Bioelectrochemistry     Hybrid Journal   (Followers: 3)
Biofuels     Hybrid Journal   (Followers: 7)
Biogeochemistry     Hybrid Journal   (Followers: 5)
BioInorganic Reaction Mechanisms     Full-text available via subscription   (Followers: 1)
Biokemistri     Open Access  
Biological Chemistry     Partially Free   (Followers: 11)
Biomedicines     Open Access   (Followers: 1)
BioMolecular Concepts     Full-text available via subscription   (Followers: 2)
Bioscience, Biotechnology, and Biochemistry     Hybrid Journal   (Followers: 6)
Biosimilars     Open Access   (Followers: 1)
Biotechnology and Applied Biochemistry     Hybrid Journal   (Followers: 17)
BMC Biochemistry     Open Access   (Followers: 8)
BMC Chemical Biology     Open Access   (Followers: 4)
Carbohydrate Polymers     Hybrid Journal   (Followers: 8)
Cell Biochemistry and Biophysics     Hybrid Journal   (Followers: 6)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 3)
Cellular Physiology and Biochemistry     Open Access   (Followers: 3)
Central European Journal of Chemistry     Hybrid Journal   (Followers: 5)
ChemBioChem     Hybrid Journal   (Followers: 2)
Chemical and Biological Technologies for Agriculture     Open Access  
Chemical Biology & Drug Design     Hybrid Journal   (Followers: 23)
Chemical Engineering Journal     Hybrid Journal   (Followers: 18)
Chemical Senses     Hybrid Journal   (Followers: 1)
Chemical Speciation and Bioavailability     Full-text available via subscription   (Followers: 1)
Chemico-Biological Interactions     Hybrid Journal   (Followers: 2)
Chemistry & Biodiversity     Hybrid Journal   (Followers: 5)
Chemistry & Biology     Full-text available via subscription   (Followers: 16)
Chemistry and Ecology     Hybrid Journal   (Followers: 1)
Clinical Biochemist Reviews     Full-text available via subscription   (Followers: 1)
Clinical Biochemistry     Hybrid Journal   (Followers: 3)
Clinical Chemistry and Laboratory Medicine     Full-text available via subscription   (Followers: 3)
Clinical Lipidology     Full-text available via subscription  
Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology     Hybrid Journal   (Followers: 5)
Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology     Hybrid Journal   (Followers: 4)
Comparative Biochemistry and Physiology Part D: Genomics and Proteomics     Hybrid Journal   (Followers: 3)
Comprehensive Biochemistry     Full-text available via subscription   (Followers: 1)
Computational Biology and Chemistry     Hybrid Journal   (Followers: 8)
Critical Reviews in Biochemistry and Molecular Biology     Hybrid Journal   (Followers: 2)
Current Chemical Biology     Hybrid Journal   (Followers: 2)
Current Opinion in Chemical Biology     Hybrid Journal   (Followers: 14)
Current Opinion in Lipidology     Hybrid Journal   (Followers: 2)
DNA Barcodes     Open Access  
Doklady Biochemistry and Biophysics     Hybrid Journal   (Followers: 2)
Doklady Chemistry     Hybrid Journal  
Egyptian Journal of Biochemistry and Molecular Biology     Full-text available via subscription  

        1 2     

Journal Cover Archives of Biochemistry and Biophysics
   Journal TOC RSS feeds Export to Zotero [11 followers]  Follow    
   Hybrid Journal Hybrid journal (It can contain Open Access articles)
     ISSN (Print) 0003-9861 - ISSN (Online) 1096-0384
     Published by Elsevier Homepage  [2563 journals]   [SJR: 1.131]   [H-I: 115]
  • Molecular mechanisms involved in the cardiovascular and neuroprotective
           effects of anthocyanins
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Sonia de Pascual-Teresa
      Anthocyanins are the main group of natural hydrosoluble pigments in plants. They introduce colouring to foods, with colours ranging from blue to red and orange. Nowadays, their importance for the Food and Pharmaceutical industries is mainly based in the existing scientific work evidencing their beneficial effects on the prevention of cardiovascular diseases and neurological conditions. Different mechanisms have been shown to be involved in those effects. The most consistent ones are related to their antihypertensive and endothelium protective activities, antiatherogenic activity and their interaction with the estrogenic receptor. In some of the existing work, studies on structure–activity relationship have been done, showing that modifications on the structure of anthocyanins, besides having an effect on their colours, have a clear incidence on their interaction with different steps in the principal pathways related to these diseases. Therefore, different colours might show different molecular mechanisms. However, in a normal diet most of these compounds are present simultaneously and, thus; they can act by different mechanisms but can rise to a common final action. Design of new food product or food supplements should take these potential synergies into consideration.


      PubDate: 2014-09-01T22:27:55Z
       
  • Baicalein modulates Nrf2/Keap1 system in both Keap1-dependent and
           Keap1-independent mechanisms
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Si Qin , Fangming Deng , Weiguo Wu , Liwen Jiang , Takaaki Yamashiro , Satoshi Yano , De-Xing Hou
      Baicalein, a major component of Scutellaria baicalensis Georgi (Huang Qin), is widely used in the traditional Chinese medicine. However, the mechanisms underlying cancer chemoprevention are still not clear. The present study aimed to clarify how baicalein modulate Nrf2/Keap1 system to exert its cytoprotection and cancer chemoprevention. In the upstream cellular signaling, baicalein stimulated the phosphorylation of MEK1/2, AKT and JNK1/2, which were demonstrated to be essential for baicalein-induced Nrf2 expression by their inhibitors. Immunoprecipitation with Nrf2 found that baicalein increased the amount of phosphorylated MEK1/2, AKT and JNK1/2 bound to Nrf2, and also stabilized Nrf2 protein by inhibiting the ubiquitination and proteasomal turnover of Nrf2. Simultaneously, baicalein down-regulated Keap1 by stimulating modification and degradation of Keap1 without affecting the dissociation of Keap1–Nrf2. Silencing Nrf2 using Nrf2 siRNA markedly reduced the ARE activity under both baseline and baicalein-induced conditions. Thus, baicalein positively modulate Nrf2/Keap1 system through both Keap1-independent and -dependent pathways. These finding provide an insight to understand the mechanisms of baicalein in cytoprotection and cancer chemoprevention.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Glucuronidation does not suppress the estrogenic activity of quercetin in
           yeast and human breast cancer cell model systems
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Roberta Ruotolo , Luca Calani , Furio Brighenti , Alan Crozier , Simone Ottonello , Daniele Del Rio
      Several plant-derived molecules, referred to as phytoestrogens, are thought to mimic the actions of endogenous estrogens. Among these, quercetin, one of the most widespread flavonoids in the plant kingdom, has been reported as estrogenic in some occasions. However, quercetin occurs in substantial amounts as glycosides such as quercetin-3-O-glucoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) in dietary sources. It is now well established that quercetin undergoes substantial phase II metabolism after ingestion by humans, with plasma metabolites after a normal dietary intake rarely exceeding nmol/L concentrations. Therefore, attributing phytoestrogenic activity to flavonoids without taking into account the fact that it is their phase II metabolites that enter the circulatory system, will almost certainly lead to misleading conclusions. With the aim of clarifying the above issue, the goal of the present study was to determine if plant-associated quercetin glycosides and human phase II quercetin metabolites, actually found in human biological fluids after intake of quercetin containing foods, are capable of interacting with the estrogen receptors (ER). To this end, we used a yeast-based two-hybrid system and an estrogen response element-luciferase reporter assay in an ER-positive human cell line (MCF-7) to probe the ER interaction capacities of quercetin and its derivatives. Our results show that quercetin-3-O-glucuronide, one of the main human phase II metabolites produced after intake of dietary quercetin, displays ERα- and ERβ-dependent estrogenic activity, the functional consequences of which might be related to the protective activity of diets rich in quercetin glycosides.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Rutin inhibits UVB radiation-induced expression of COX-2 and iNOS in
           hairless mouse skin: p38 MAP kinase and JNK as potential targets
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Ki-Seok Choi , Joydeb Kumar Kundu , Kyung-Soo Chun , Hye-Kyung Na , Young-Joon Surh
      Exposure to ultraviolet B (UVB) radiation, a complete environmental carcinogen, induces oxidative and inflammatory skin damage, thereby increasing the risk of skin carcinogenesis. The antioxidant and anti-inflammatory activities of a wide variety of plant polyphenols have been reported. Rutin (3-rhamnosyl-glucosylquercetin), a polyphenol present in many edible plants, possesses diverse pharmacological properties including antioxidant, anti-inflammatory, antimutagenic and anticancer activities. The present study was aimed to investigate the effects of rutin on UVB-induced inflammation in mouse skin in vivo. Topical application of rutin onto the dorsal skin of female HR-1 hairless mice 30min prior to UVB irradiation diminished epidermal hyperplasia and the levels of proteins modified by 4-hydroxynonenal, which is a biochemical hallmark of lipid peroxidation. Topical application of rutin also significantly inhibited UVB-induced expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), two representative inflammatory enzymes, in hairless mouse skin. Rutin inhibited the DNA binding of activator protein-1 (AP-1) and phosphorylation of signal transducer and activator of transcription-3 (STAT3) in mouse skin exposed to UVB. Moreover, rutin attenuated UVB-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun-N-terminal kinase (JNK). Pharmacological inhibition of p38 MAP kinase and JNK decreased UVB-induced expression of COX-2 in mouse skin. Taken together, these findings suggest that rutin exerts anti-inflammatory effects in UVB-irradiated mouse skin by inhibiting expression of COX-2 and iNOS, which is attributable to its suppression of p38 MAP kinase and JNK signaling responsible for AP-1 activation.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Green coffee polyphenols do not attenuate features of the metabolic
           syndrome and improve endothelial function in mice fed a high fat diet
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): J.D. Li Kwok Cheong , K.D. Croft , P.D. Henry , V. Matthews , J.M. Hodgson , N.C. Ward
      We have investigated the effects of the major polyphenol in coffee, chlorogenic acid (CGA), on obesity, glucose intolerance, insulin resistance, systemic oxidative stress and endothelial dysfunction in a mouse model of the metabolic syndrome. Thirty C57BL6 mice were randomly divided into (n =10/group) (i) normal diet (ND), (ii) high fat diet (HFD), or (iii) high fat diet supplemented with 0.5% w/w green coffee bean extract (GCE) rich in chlorogenic acid (HFD+GCE). The high fat diet consisted of 28% fat and all animals were maintained on their diets for 12weeks. The mice fed a HFD and HFD+GCE displayed symptoms of the metabolic syndrome compared to their normal fed counterparts, although no endothelial dysfunction was detected in the abdominal aortas after 12weeks. GCE did not attenuate HFD-induced obesity, glucose intolerance, insulin resistance or systemic oxidative stress. Furthermore, GCE did not protect against ex vivo oxidant (hypochlorous acid)-induced endothelial dysfunction.


      PubDate: 2014-09-01T22:27:55Z
       
  • Absorption, distribution, metabolism, and excretion of isoflavonoids after
           soy intake
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Adrian A. Franke , Jennifer F. Lai , Brunhild M. Halm
      Soy is the major source of dietary exposure to isoflavonoids (IFLs). Accumulating evidence supports a role for soy and IFLs in the protection against many chronic diseases including cancer. After soy intake we found a biphasic IFL appearance pattern in plasma as well as in urine that we suggest to be due to IFL absorption in the small intestine (ca. 10%) during the first 2h after intake and IFL absorption in the large intestine (ca. 90%) 4–6h after intake. While each IFL disappears from the circulation at different times excellent correlations between urinary and circulating IFL values were discovered and algorithms to convert urinary excretion values into circulating levels were established. We suggest the term ‘apparent bioavailability’ when using urinary data to describe IFL exposure. The IFL bioavailability was found to be influenced by gut bacteria, oral antibiotic treatment (OABX), and an individual’s age and health status. While daidzein (DE) and genistein start to be absorbed minutes after intake, equol (EQ) appears in plasma only after a minimum of 8h following soy intake owing to the required transit time of DE to the colon where the conversion of DE to EQ takes place by intestinal microbiota. We have also shown that the apparent IFL bioavailability is higher in children than adults, higher in healthy versus non-healthy individuals, and decreased in children but increased in adults during OABX. Finally, we propose to use a urinary EQ/DE ratio of 0.018 with a DE threshold to identify EQ producers. With this cutoff definition we observed that EQ production is inconsistent over time in 5–30% of both premenopausal and postmenopausal women.


      PubDate: 2014-09-01T22:27:55Z
       
  • Consumption of both low and high (−)-epicatechin apple puree
           attenuates platelet reactivity and increases plasma concentrations of
           nitric oxide metabolites: A randomized controlled trial
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Amy Gasper , Wendy Hollands , Amelie Casgrain , Shikha Saha , Birgit Teucher , Jack R. Dainty , Dini P. Venema , Peter C. Hollman , Maarit J. Rein , Rebecca Nelson , Gary Williamson , Paul A. Kroon
      We hypothesised that consumption of flavanol-containing apple puree would modulate platelet activity and increase nitric oxide metabolite status, and that high flavanol apple puree would exert a greater effect than low flavanol apple puree. 25 subjects consumed 230g of apple puree containing 25 and 100mg epicatechin (low and high flavanol apple puree, respectively) and aspirin (75mg) in random order. Measurements were made at baseline, acutely after treatment (2, 6 and 24h), and after 14d of treatment. Low flavanol apple puree significantly attenuated ADP and epinephrine-induced integrin-β3 expression 2h and 6h after consumption and ADP and epinephrine-induced P-selectin expression within 2h of consumption. High flavanol apple puree attenuated epinephrine and ADP-induced integrin-β3 expression after 2 and 6h. ADP and epinephrine-induced integrin-β3 expression was significantly attenuated 2, 6 and 24h after consumption of aspirin, whilst 14 d aspirin consumption attenuated collagen-induced P-selectin expression only. The plasma total nitric oxide metabolite conc. was significantly increased 6h after consumption of both low and high flavanol apple purees. In conclusion, consumption of apple purees containing ⩾25 or 100mg flavanols transiently attenuated ex vivo integrin-β3 and P-selectin expression and increased plasma nitric oxide metabolite conc. in healthy subjects, but the effect was not enhanced for the high flavanol apple puree.


      PubDate: 2014-09-01T22:27:55Z
       
  • Polyphenols and mitochondria: An update on their increasingly emerging
           ROS-scavenging independent actions
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Cristian Sandoval-Acuña , Jorge Ferreira , Hernán Speisky
      Polyphenols, ubiquitously present in fruits and vegetables, have been traditionally viewed as antioxidant molecules. Such contention emerged, mainly from their well established in vitro ability to scavenge free radicals and other reactive oxygen species (ROS). During the last decade, however, increasing evidence has emerged supporting the ability of certain polyphenols to also exert numerous ROS-scavenging independent actions. Although the latter can comprise the whole cell, particular attention has been placed on the ability of polyphenols to act, whether favorably or not, on a myriad of mitochondrial processes. Thus, some particular polyphenols are now recognized as molecules capable of modulating pathways that define mitochondrial biogenesis (i.e., inducing sirtuins), mitochondrial membrane potential (i.e., mitochondrial permeability transition pore opening and uncoupling effects), mitochondrial electron transport chain and ATP synthesis (i.e., modulating complexes I to V activity), intra-mitochondrial oxidative status (i.e., inhibiting/inducing ROS formation/removal enzymes), and ultimately mitochondrially-triggered cell death (i.e., modulating intrinsic-apoptosis). The present review describes recent evidence on the ability of some polyphenols to modulate each of the formerly mentioned pathways, and discusses on how, by acting on such mitochondrial processes, polyphenols may afford protection against those mitochondrial damaging events that appear to be key in the cellular toxicity induced by various xenobiotics as well as that seen during the development of several ROS-related diseases.


      PubDate: 2014-09-01T22:27:55Z
       
  • Downregulation of tumor necrosis factor and other proinflammatory
           biomarkers by polyphenols
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Subash C. Gupta , Amit K. Tyagi , Priya Deshmukh-Taskar , Myriam Hinojosa , Sahdeo Prasad , Bharat B. Aggarwal
      Human tumor necrosis factor (TNF), first isolated by our group as an anticancer agent, has been now shown to be a primary mediator of inflammation. Till today 19 different members of the TNF superfamily which interact with 29 different receptors, have been identified. Most members of this family exhibit pro-inflammatory activities, in part through the activation of the transcription factor, nuclear factor-kappaB (NF-κB). Thus TNF and the related pro-inflammatory cytokines have been shown to play a key role in most chronic diseases such as cancer, rheumatoid arthritis, cardiovascular diseases, psoriasis, neurologic diseases, Crohn’s disease, and metabolic diseases. Therefore, agents that can modulate the TNF-mediated inflammatory pathways may have potential against these pro-inflammatory diseases. Although blockers of TNF-α, such as infliximab (antibody against TNF-α), adalimumab (humanized antibody against TNF-α), and etanercept (soluble form of TNFR2) have been approved for human use, these blockers exhibit numerous side effects. In this review, we describe various plant-derived polyphenols that can suppress TNF-α activated inflammatory pathways both in vitro and in vivo. These polyphenols include curcumin, resveratrol, genistein, epigallocatechin gallate, flavopiridol, silymarin, emodin, morin isoliquiritigenin, naringenin, ellagic acid, apigenin, kaempferol, catechins, myricetin, xanthohumol, fisetin, vitexin, escin, mangostin and others. Thus these polyphenols are likely to have potential against various pro-inflammatory diseases.


      PubDate: 2014-09-01T22:27:55Z
       
  • Unravelling of the health effects of polyphenols is a complex puzzle
           complicated by metabolism
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Peter C.H. Hollman
      Plant metabolism creates complex mixtures of polyphenols in plant foods. Epidemiology and human trials reduced this complexity, by studying specific foods; subclasses of polyphenols; individual polyphenols, or total antioxidant capacity (TAC). This implies the following assumptions: (1) a limited number of potent polyphenols exists; (2) well-defined natural potent mixtures of polyphenols exist; (3) polyphenols share a common biological activity (e.g. antioxidant activity). To find potent polyphenols (1st assumption), in vitro screening has been widely applied, but most published results are of limited use because metabolism, changing biological activity profoundly, has frequently not been considered. The abundant anecdotal evidence for natural potent mixtures of polyphenols (2nd assumption) on the internet is very hard to verify. Additionally, cross-cultural studies have revealed the potency of e.g. cocoa. Polyphenols share the antioxidant phenolic group which inspired researchers to measure their antioxidant activity, thus greatly reducing complexity (3rd assumption). Unfortunately, the elegant antioxidant hypothesis has to be rejected, because poor absorption and extensive metabolism annihilate any contribution to the endogenous body antioxidants. In conclusion, the above assumptions are hard to verify, and no quick answers are to be expected. Future research should focus on structure–activity relations at nanomolar levels and explore metabolomics.


      PubDate: 2014-09-01T22:27:55Z
       
  • Uptake and metabolism of (−)-epicatechin in endothelial cells
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Ana Rodriguez-Mateos , Natalia Toro-Funes , Tania Cifuentes-Gomez , Miriam Cortese-Krott , Christian Heiss , Jeremy P.E. Spencer
      Accumulating evidence suggest that diets rich in cocoa flavanols may have beneficial effects on cardiovascular health. The major cocoa flavanol monomer, (−)-epicatechin (EC), is readily absorbed and circulates primarily as glucuronidated, sulfated, and O-methylated metabolites in human plasma. However, cellular metabolism, for example in endothelial cells, is less well defined. In the present study we detail the uptake and cellular metabolism of EC and its major in vivo metabolites, (−)-epicatechin-3′-β-d-glucuronide (E3G), (−)-epicatechin-3′-sulfate (E3S), 3′-O-methyl-(−)-epicatechin-5-sulfate (3ME5S), and 3′-O-methyl-(−)-epicatechin-7-sulfate (3ME7S) in human endothelial (HUVEC), liver (HepG2) and intestinal epithelial cells (Caco-2 monolayer). Our results indicate that EC associates with HUVECs, leading to its intracellular metabolism to 3ME7G and 3ME7S. In contrast, none of the metabolites were taken up by the cells. The metabolic rate and pattern of metabolism in HUVECs was similar to that observed in HepG2 cells, whilst in Caco-2 cells EC was metabolized to E3G, 3ME5G, 3ME7G, 4ME5G, 4ME7G and 3ME7S. Our data support the notion that endothelial cells may contribute significantly to EC metabolism. However, major human circulating metabolites are not accounted for in these model systems underscoring that caution should be taken when drawing conclusions on in vivo flavanol metabolism from in vitro experiments.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Special issue “polyphenols and health”
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Junji Terao , Helmut Sies



      PubDate: 2014-09-01T22:27:55Z
       
  • Improved high sensitivity analysis of polyphenols and their metabolites by
           nano-liquid chromatography–mass spectrometry
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Landon Wilson , Ali Arabshahi , Brigitte Simons , Jeevan K. Prasain , Stephen Barnes
      This study was conducted to assess the value of a high resolution, high mass accuracy time-of-flight analyzer in combination with nanoliquid chromatography for the analysis of polyphenols and their metabolites. The goal was to create a method that utilizes small volumes of biological fluids and provides a significant improvement in sensitivity compared with existing methods. Accordingly, nanoLC–MS and nanoLC-pseudo-multiple reaction monitoring (MRM) methods were developed that had a lower limit of quantification of 0.5nM for several polyphenols and were linear over 2–3 orders of magnitude (R 2 >0.999). Using urine samples, the ability to observe and quantify polyphenols in such a complex biological fluid depended on much narrower mass windows (0.050amu or less) on a TOF analyzer than those used on a quadrupole analyzer (0.7amu). Although a greater selectivity was possible with the low mass resolution of a triple quadrupole instrument using the MRM approach, for the daidzein metabolite O-DMA, a chromatographically resolvable second peak could only be substantially reduced by using a 0.01amu mass window. The advantage of a TOF analyzer for product ion data is that the whole MSMS spectrum is collected at high mass accuracy and MRM experiments are conducted in silico after the analysis.


      PubDate: 2014-09-01T22:27:55Z
       
  • Prenylation modulates the bioavailability and bioaccumulation of dietary
           flavonoids
    • Abstract: Publication date: 1 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 559
      Author(s): Junji Terao , Rie Mukai
      Prenylflavonoids are distributed widely in the plant kingdom and have attracted appreciable attention because of their potential benefits for human health. Prenylation may be a promising tool for applying the biological functions of flavonoids to clinical uses. The bioavailability and bioaccumulation of prenylflavonoids have not been clarified, but extensive studies have been accomplished on their biological functions. This review provides current knowledge on the bioavailability of prenylflavonoids, including their absorption and metabolism in the intestine, as well as their bioaccumulation in specific tissues. Despite higher uptake into epithelial cells of the digestive tract, the bioavailability of single-dose prenylflavonoids seems to be lower than that of the parent flavonoids. Efflux from epithelial cells to the blood circulation is likely to be restricted by prenyl groups, resulting in insufficient increase in the plasma concentration. Rodent studies have revealed that prenylation enhances accumulation of naringenin in muscle tissue after long-term feeding; and that prenylation accelerates accumulation of quercetin in liver tissue. Efflux from hepatocytes to blood and enterohepatic circulations may be restricted by prenyl groups, thereby promoting slow excretion of prenylflavonoids from the blood circulation and efficient uptake to tissues. The hepatotoxicity and other deleterious effects, taken together with beneficial effects, should be considered because unexpectedly high accumulation may occur in some tissues after long-term supplementation.
      Graphical abstract image Highlights

      PubDate: 2014-09-01T22:27:55Z
       
  • Investigation on the influence of
           (Z)-3-(2-(3-chlorophenyl)hydrazono)-5,6-dihydroxyindolin-2-one (PT2) on
           β-amyloid(1–40) aggregation and toxicity
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Marco Catto , Fabio Arnesano , Gerardo Palazzo , Angelo De Stradis , Vincenza Calò , Maurizio Losacco , Rosa Purgatorio , Francesco Campagna
      In Alzheimer’s disease (AD), native Aβ protein monomers aggregate through the formation of a variety of water-soluble, toxic oligomers, ultimately leading to insoluble fibrillar deposits. The inhibition of oligomers formation and/or their dissociation into non-toxic monomers, are considered an attractive strategy for the prevention and treatment of AD. A number of studies have demonstrated that small molecules, containing single or multiple (hetero)aromatic rings, can inhibit protein aggregation, being potentially effective in AD treatment. Starting from previously reported data on the antiamyloidogenic activity of a series of 3-hydrazonoindolinones, compound PT2 was selected to deeply investigate the inhibitory mechanism in the Aβ aggregation cascade. We compared data from DLS, NMR, CD, TEM and ThT fluorescence measures to ascertain the interactions with amyloidogenic species formed in vitro during the aggregation process, and confirmed this feature with cell viability tests on HeLa cultured cells. PT2 was effective in disrupting toxic oligomers and mature amyloid fibrils, stabilizing Aβ as non-toxic, β-sheet arranged, ThT-insensitive protofilaments. It also strongly reduced cellular toxicity caused by Aβ and showed good antioxidant properties in two radical scavenging tests. Taken together, these data confirmed that PT2 is a small molecule inhibitor of Aβ oligomerization and toxicity, displaying also additional activity as antioxidant.
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      PubDate: 2014-09-01T22:27:55Z
       
  • G-quadruplex formation of FXYD1 pre-mRNA indicates the possibility of
           regulating expression of its protein product
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Hansraj Dhayan , Anwar R. Baydoun , Andreas Kukol
      G-quadruplexes are higher-order nucleic acid structures formed of square-planar arrangements of four guanine bases held together by Hoogsteen-type hydrogen bonds. Stacks of guanine tetrads are stabilised by intercalating potassium ions. FXYD1 encodes for phospholemman, a regulatory subunit of the cardiac Na+/K+-ATPase. Computational sequence analysis of FXYD1 pre-mRNA predicted the formation of stable intramolecular G-quadruplexes in human and orthologue sequences. Multiple sequence alignment indicated that G-rich sequences are conserved in evolution suggesting a potential role of G-quadruplexes in FXYD1 gene expression. The existence of a non-functional alternative splicing product indicated that the G-quadruplex formation may control alternative splicing. Quadruplex formation of human and bovine oligonucleotides was confirmed in vitro by native polyacrylamide gel electrophoresis and intrinsic fluorescence emission spectroscopy. Taking together the evolutionary conservation of G-quadruplex forming sequences with the confirmation of G-quadruplex formation in vitro by two FXYD1 homologues the results point to a potential role of these structures in regulating the expression of FXYD1 and thus regulate indirectly the activity of the cardiac Na+/K+-ATPase.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Expression of organic osmolyte transporters in cultured rat astrocytes and
           rat and human cerebral cortex
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Jessica Oenarto , Boris Görg , Michael Moos , Hans-Jürgen Bidmon , Dieter Häussinger
      This study characterizes the expression of the osmolyte transporters betaine/γ-amino-n-butyric acid (GABA) transporter (BGT-1), the taurine transporter (TauT) and the sodium-dependent myo-inositol transporter (SMIT) in various rat brain cells in culture and in rat and human cerebral cortex in situ. Osmolyte transporter expression greatly differed between cultured brain cells with highest mRNA expression levels for SMIT in astrocytes and TauT in neurons. BGT-1 mRNA and protein were expressed in microglia but not in astrocytes and neurons. In rat and human cerebral cortex, SMIT was expressed in astrocytes and TauT was found in neurons. Osmolyte transporter expression was subject to regulation by factors relevant for hepatic encephalopathy (HE). Hypoosmolarity, NH4Cl (0.5–5mmol/l), diazepam (10μmol/l) and TNFα (10ng/ml) time-dependently decreased mRNA expression of SMIT and/or TauT in cultured astrocytes. NH4Cl-induced SMIT/TauT mRNA expression changes were sensitive to inhibitors of glutamine synthetase and NADPH oxidase. In rat cerebral cortex, SMIT mRNA expression decreased after portal vein ligation or ammonium acetate injection probably due to astrocyte swelling in these HE animal models. It is concluded that osmolyte transporters are heterogeneously expressed in brain and are subject to regulation by HE-relevant factors.


      PubDate: 2014-09-01T22:27:55Z
       
  • Low-molecular-weight thiols in plants: Functional and analytical
           implications
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Micaela Pivato , Marta Fabrega-Prats , Antonio Masi
      Low-molecular-weight (LMW) thiols are a class of highly reactive compounds massively involved in the maintenance of cellular redox homeostasis. They are implicated in plant responses to almost all stress factors, as well as in the regulation of cellular metabolism. The most studied LMW thiols are glutathione and its biosynthetically related compounds (cysteine, γ-glutamylcysteine, cysteinylglycine, and phytochelatins). Other LMW thiols are described in the literature, such as thiocysteine, cysteamine, homocysteine, lipoic acid, and many species-specific volatile thiols. Here, we review the known LMW thiols in plants, briefly describing their physico-chemical properties, their relevance in post-translational protein modification, and recently-developed thiol detection methods. Current research points to a huge thiol biodiversity in plants and many species-specific and organ-specific thiols remain to be identified. Recent advances in technology should help researchers in this very challenging task, helping us to decipher the roles of thiols in plant metabolism.
      Graphical abstract image

      PubDate: 2014-09-01T22:27:55Z
       
  • Atmospheric-pressure plasma jet induces DNA double-strand breaks that
           require a Rad51-mediated homologous recombination for repair in
           Saccharomyces cerevisiae
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Yoonna Lee , Kangil Kim , Kyu-Tae Kang , Jong-Soo Lee , Sang Sik Yang , Woo-Hyun Chung
      Non-thermal plasma generated under atmospheric pressure produces a mixture of chemically reactive molecules and has been developed for a number of biomedical applications. Recently, plasma jet has been proposed as novel cancer therapies based on the observation that free radicals generated by plasma jet induce mitochondria-mediated apoptotic cell death. We show here that air plasma jet induces DNA double-strand breaks (DSBs) in yeast chromosomes leading to genomic instability and loss of viability, which are alleviated by Rad51, the yeast homolog of E scherichia coli RecA recombinase, through DNA damage repair by a homologous recombination (HR) process. Hypersensitivity of rad51 mutant to air plasma was not restored by antioxidant treatment unlike sod1 mutant that was highly sensitive to reactive oxygen species (ROS) challenge, suggesting that plasma jet induces DSB-mediated cell death independent of ROS generation. These results may provide a new insight into the mechanism of air plasma jet-induced cell death.


      PubDate: 2014-09-01T22:27:55Z
       
  • Structural and biochemical analysis of a type II free
           methionine-R-sulfoxide reductase from Thermoplasma acidophilum
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Hyun Sook Kim , Geun-Hee Kwak , Kitaik Lee , Chang-Hwa Jo , Kwang Yeon Hwang , Hwa-Young Kim
      Free methionine-R-sulfoxide reductase (fRMsr) enzymes only reduce the free form of methionine-R-sulfoxide and can be grouped into two types with respect to the number of conserved Cys residues in the active sites. In this work, the crystal structures of type II fRMsr from Thermoplasma acidophilum (TafRMsr), which contains two conserved Cys, have been determined in native form and in a complex with the substrate. The overall structure of TafRMsr consists of a central β-sheet encompassed by a two-α-helix bundle flanking on one side and one small α-helix on the other side. Based on biochemical and growth complementation assays, Cys84 is demonstrated to be the catalytic Cys. The data also show that TafRMsr functions as an antioxidant protein. Structural analyses reveal insights into substrate recognition and orientation, conformational changes in the active site during substrate binding, and the role of active site residues in substrate binding. A model for the catalytic mechanism of type II TafRMsr is suggested, in which intramolecular disulfide bond formation is not involved. In addition, the biochemical, enzymatic, and structural properties of type II TafRMsr are compared with those of type I enzymes.


      PubDate: 2014-09-01T22:27:55Z
       
  • High-glucose-induced CARM1 expression regulates apoptosis of human retinal
           pigment epithelial cells via histone 3 arginine 17 dimethylation: Role in
           diabetic retinopathy
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Dong-il Kim , Min-jung Park , Seul-ki Lim , Joo-hee Choi , Jong-choon Kim , Ho-jae Han , Tapas K. Kundu , Jae-il Park , Kyung-chul Yoon , Sang-woo Park , Jong-sung Park , Young-ran Heo , Soo-hyun Park
      Hyperglycemia-induced apoptosis of retinal pigment epithelial (RPE) cells is considered to be involved in the progression of diabetic retinopathy. Histone arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) has emerged as an important histone modification involved in gene regulation. However, the role of PRMTs in diabetic retinopathy has not been elucidated. Here, we found that expression of coactivator-associated arginine methyltransferase 1 (CARM1; also known as PRMT4) was increased in the high-glucose treated human RPE cell line ARPE-19 and in the RPE layer of streptozotocin-treated rats. In addition, high-glucose induced apoptosis in ARPE-19 cells. To determine the function of CARM1 on RPE cell apoptosis, we performed gain- and loss-of-function studies. CARM1 overexpression increased apoptosis of RPE cells. In contrast, silencing of CARM1 expression by siRNA and pharmacological inhibition of CARM1 activity abolished high-glucose-induced RPE cell apoptosis. Furthermore, we found that inhibition of histone 3 arginine 17 (H3R17) asymmetric dimethylation attenuates both CARM1- and high-glucose-induced apoptosis in RPE cells. Together, these results show that high-glucose-induced CARM1 expression increases RPE cell apoptosis via H3R17 asymmetric dimethylation. Strategies to reduce CARM1 expression or enzymatic activity could be used to prevent apoptosis of RPE cells in the progression of diabetic retinopathy.


      PubDate: 2014-09-01T22:27:55Z
       
  • Disrupted calcium homeostasis is involved in elevated zinc ion-induced
           photoreceptor cell death
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Dadong Guo , Yuxiang Du , Qiuxin Wu , Wenjun Jiang , Hongsheng Bi
      Zinc (Zn), the second abundant trace element in living organisms, plays an important role in regulating cell metabolism, signaling, proliferation, gene expression and apoptosis. Meanwhile, the overload of Zn will disrupt the intracellular calcium homeostasis via impairing mitochondrial function. However, the specific molecular mechanism underlying zinc-induced calcium regulation remains poorly understood. In the present study, using zinc chloride (ZnCl2) as a stressor, we investigated the effect of exogenous Zn2+ in regulating murine photoreceptor cell viability, reactive oxygen species (ROS), cell cycle distribution and calcium homeostasis as well as plasma membrane calcium ATPase (PMCA) isoforms (PMCA1 and PMCA2, i.e., ATP2B1, ATP2B2) expression. We found that the exogenous Zn2+ in the exposure range (31.25–125.0μmol/L) results in the overgeneration of ROS, cell cycle arrest at G2/M phases, elevation of cytosolic [Ca2+], inactivation of Ca2+-ATPase and reduction of both PMCA1 and PMCA2 in 661Wcells, and thus induces cell death. In conclusion, ZnCl2 exposure can elevate the cytosolic [Ca2+], disrupt the intracellular calcium homeostasis, further initiate Ca2+-dependent signaling pathway in 661Wcells, and finally cause cell death. Our results will facilitate the understanding of cell death induced by the zinc ion-mediated calcium homeostasis disruption.
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      PubDate: 2014-09-01T22:27:55Z
       
  • Dynamic profile and adipogenic role of growth differentiation factor 5
           (GDF5) in the differentiation of 3T3-L1 preadipocytes
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Zhou Pei , Yi Yang , Wieland Kiess , Chengjun Sun , Feihong Luo
      Adipocyte differentiation is key to determining the number of adipocytes during the development of obesity. Recent studies have shown that growth differentiation factor-5 (GDF5) promotes brown adipogenesis, however its role in white adipogenesis is still uncertain. The aim of the present study was to investigate the effect of GDF5 on white adipogenesis using 3T3-L1 preadipocyte model. In the present study, GDF5 was found to be differentially regulated during adipocyte differentiation. GDF5 protein increased the differentiation of 3T3-L1 preadipocytes, especially when these cells were exposed to hormone cocktails without insulin. During adipogenesis, GDF5 enhanced the expression of genes related to adipocyte differentiation and caused cells to enter the S phase. Short-hairpin-RNA knockdown of GDF5 in 3T3-L1 cells was found to prevent adipogenesis induced by a standard hormone cocktail and to downregulate the expression of adipocyte genes and proteins, this impairment could be partly rescued by GDF5 protein. Collectively, these results suggest that GDF5 can promote progression of the cell-cycle and increase numbers of cells in S phase, GDF5 might play a critical role in 3T3-L1 preadipocyte differentiation.


      PubDate: 2014-09-01T22:27:55Z
       
  • Inhibition of Escherichia coli tryptophan indole-lyase by tryptophan
           homologues
    • Abstract: Publication date: 15 October 2014
      Source:Archives of Biochemistry and Biophysics, Volume 560
      Author(s): Quang T. Do , Giang T. Nguyen , Victor Celis , Robert S. Phillips
      We have designed, synthesized and evaluated homotryptophan analogues as possible mechanism-based inhibitors for Escherichia coli tryptophan indole-lyase (tryptophanase, TIL, E.C. 4.1.99.1). As a quinonoid structure is an intermediate in the reaction mechanism of TIL, we anticipated that homologation of the physiological substrate, l-Trp would provide analogues resembling the transition state for β-elimination, and potentially inhibit TIL. Our results demonstrate that l-homotryptophan (1a) is a moderate competitive inhibitor of TIL, with Ki =67μM, whereas l-bishomotryptophan (1b) displays more potent inhibition, with Ki =4.7μM. Pre-steady-state kinetics indicated the formation of an external aldimine and quinonoid with 1a, but only the formation of an external aldimine for 1b, suggesting differences in the inhibition mechanism. These results demonstrate that formation of a quinonoid complex is not required for strong inhibition. In addition, the Trp analogues were evaluated as inhibitors of Salmonella typhimurium Trp synthase. Our results indicate that compound 1b is at least 25-fold more selective toward TIL than Trp synthase. We report that compound 1b is comparable to the most potent inhibitor previously reported, while displaying high selectivity for TIL. Thus, 1b is a potential lead for the development of novel antibacterials.
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      PubDate: 2014-09-01T22:27:55Z
       
  • Structural dissection of the C-terminal sterile alpha motif (SAM) of human
           p73
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): José L. Neira
      The alpha splice variant of p73 (p73α), a homologue of the tumour suppressor p53, has at its C terminus a sterile alpha motif (SAM); this domain, SAMp73, is involved in lipid binding and it is thought to mediate in protein–protein interactions. SAMp73 is composed of five helices (α1–α5). In this work, we dissected SAMp73 in fragments encompassing the different helices, to study the conformational stability of the isolated elements of secondary structure. There was no evidence of stable residual helical structure in the isolated α1, α4 and α5 helices in aqueous solution, as shown by 2D-1H NMR and far-UV CD spectroscopies; those helices acquired native-like helical structure in the presence of 40% trifluoroethanol (TFE). The population of helical structure in α5 seemed to be driven by the indole moiety of Trp542, and it was enhanced by the presence of α4. On the other hand, helices α2 and 310(α3) had a tendency to self-associate even in TFE–water solutions. However, the short, aggregation-prone 310(α3) helix was key to attain the native-like fold of SAMp73, as suggested by experiments with non-covalent complexes among the peptides.
      Graphical abstract image

      PubDate: 2014-08-03T20:41:01Z
       
  • A novel chemopreventive mechanism for a traditional medicine: East Indian
           sandalwood oil induces autophagy and cell death in proliferating
           keratinocytes
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Sally E. Dickinson , Erik R. Olson , Corey Levenson , Jaroslav Janda , Jadrian J. Rusche , David S. Alberts , G. Timothy Bowden
      One of the primary components of the East Indian sandalwood oil (EISO) is α-santalol, a molecule that has been investigated for its potential use as a chemopreventive agent in skin cancer. Although there is some evidence that α-santalol could be an effective chemopreventive agent, to date, purified EISO has not been extensively investigated even though it is widely used in cultures around the world for its health benefits as well as for its fragrance and as a cosmetic. In the current study, we show for the first time that EISO-treatment of HaCaT keratinocytes results in a blockade of cell cycle progression as well as a concentration-dependent inhibition of UV-induced AP-1 activity, two major cellular effects known to drive skin carcinogenesis. Unlike many chemopreventive agents, these effects were not mediated through an inhibition of signaling upstream of AP-1, as EISO treatment did not inhibit UV-induced Akt or MAPK activity. Low concentrations of EISO were found to induce HaCaT cell death, although not through apoptosis as annexin V and PARP cleavage were not found to increase with EISO treatment. However, plasma membrane integrity was severely compromised in EISO-treated cells, which may have led to cleavage of LC3 and the induction of autophagy. These effects were more pronounced in cells stimulated to proliferate with bovine pituitary extract and EGF prior to receiving EISO. Together, these effects suggest that EISO may exert beneficial effects upon skin, reducing the likelihood of promotion of pre-cancerous cells to actinic keratosis (AK) and skin cancer.


      PubDate: 2014-08-03T20:41:01Z
       
  • CD24 regulates stemness and the epithelial to mesenchymal transition
           through modulation of Notch1 mRNA stability by p38MAPK
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Juyeon Lim , Kyung-min Lee , Jaekyung Shim , Incheol Shin
      We report here that CD24 knockdown resulted in decreased expression of Notch1 in MCF-7 cells. CD24-downstream p38MAPK was shown to regulate Notch1 at the level of mRNA stability. We also found that CD24-mediated cell migration, invasion, mammosphere formation, and drug resistance was regulated by its downstream target Notch1. Together, our results indicate that CD24 may regulate the epithelial to mesenchymal transition and stemness through Notch1 signaling in breast cancer cells.


      PubDate: 2014-07-30T20:25:07Z
       
  • Identification of important residues of insulin-like peptide 5 and its
           receptor RXFP4 for ligand–receptor interactions
    • Abstract: Publication date: Available online 18 July 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Xin-Yi Wang , Yu-Qi Guo , Xiao-Xia Shao , Ya-Li Liu , Zeng-Guang Xu , Zhan-Yun Guo
      Insulin-like peptide 5 (INSL5) is an insulin/relaxin superfamily peptide involved in the regulation of glucose homeostasis by activating its receptor RXFP4, which can also be activated by relaxin-3 in vitro. To determine the interaction mechanism of INSL5 with its receptor RXFP4, we studied their electrostatic interactions using a charge-exchange mutagenesis approach. First, we identified three negatively charged extracellular residues (Glu100, Asp104 and Glu182) in human RXFP4 that were important for receptor activation by wild-type INSL5. Second, we demonstrated that two positively charged B-chain Arg residues (B13Arg and B23Arg) in human INSL5 were involved in receptor binding and activation. Third, we proposed probable electrostatic interactions between INSL5 and RXFP4: the B-chain central B13Arg of INSL5 interacts with both Asp104 and Glu182 of RXFP4, meanwhile the B-chain C-terminal B23Arg of INSL5 interacts with both Glu100 and Asp104 of RXFP4. The present electrostatic interactions between INSL5 and RXFP4 were similar to our previously identified interactions between relaxin-3 and RXFP4, but had subtle differences that might be caused by the different B-chain C-terminal conformations of relaxin-3 and INSL5 because a dipeptide exchange at the B-chain C-terminus significantly decreased the activity of INSL5 and relaxin-3 to receptor RXFP4.
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      PubDate: 2014-07-26T20:02:45Z
       
  • Oxidatively generated base damage to cellular DNA by hydroxyl radical and
           one-electron oxidants: Similarities and differences
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Jean Cadet , J. Richard Wagner
      Hydroxyl radical ( OH) and one-electron oxidants that may be endogenously formed through oxidative metabolism, phagocytosis, inflammation and pathological conditions constitute the main sources of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UV light, high intensity UV laser, ionizing radiation) and chemicals may also induce oxidatively generated damage to DNA. Emphasis is placed in this short review article on the mechanistic aspects of OH and one-electron oxidant-mediated formation of single and more complex damage (tandem lesions, intra- and interstrand cross-links, DNA–protein cross-links) in cellular DNA arising from one radical hit. This concerns DNA modifications that have been accurately measured using suitable analytical methods such as high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Evidence is provided that OH and one-electron oxidants after generating neutral radicals and base radical cations respectively may partly induce common degradation pathways. In addition, selective oxidative reactions giving rise to specific degradation products of OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified.


      PubDate: 2014-07-26T20:02:45Z
       
  • Identification of microRNAs involved in the modulation of pro-angiogenic
           factors in atherosclerosis by a polyphenol-rich extract from propolis
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Alejandro Cuevas , Nicolás Saavedra , Marcela F. Cavalcante , Luis A. Salazar , Dulcineia S.P. Abdalla
      New vessel formation plays a critical role in the progression and vulnerability of atherosclerotic lesions. It has been shown that polyphenols from propolis attenuate the progression of atherosclerosis and also exert inhibitory effects on angiogenic factors. However, the mechanisms underlying these effects are not completely understood. Thus, this study aimed to identify microRNAs (miRNAs) involved in the modulation of pro-angiogenic factors in the atherosclerotic plaques of LDL receptor gene knockout mice treated with a polyphenol-rich extract of Chilean propolis. The progression of the atherosclerotic lesions was significantly attenuated in treated mice compared with control mice. Using microarray analysis and a bioinformatic approach, we identified 29 differentially expressed miRNAs. Many of these miRNAs were involved in biological processes associated with angiogenesis, such as the cell cycle, cell migration, cell growth and proliferation. Among them, three miRNAs (miR-181a, miR-106a and miR-20b) were over-expressed and inversely related to the expression of Vegfa (vascular endothelial growth factor A) and Hif1a (hypoxia inducible factor 1 alpha). In addition, VEGF-A protein expression was attenuated in histological sections obtained from the aortic sinuses of treated mice. VEGFA is a key pro-angiogenic factor in atherosclerotic plaques, and Hif1a, which is expressed in the necrotic nucleus of the atheroma, is its main inducer. We found a correlation between the over-expression of miR-181a, miR-106a and miR-20b and their target genes, Hif1a and Vegfa, which is consistent with attenuation of the atherosclerotic lesion. In conclusion, our data analysis provides evidence that the anti-angiogenic effects of polyphenols from Chilean propolis can be modulated by miRNAs, in particular miR-181a, miR-106a and miR-20b.


      PubDate: 2014-07-26T20:02:45Z
       
  • Luteolin modulates expression of drug-metabolizing enzymes through the AhR
           and Nrf2 pathways in hepatic cells
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Tianshun Zhang , Yuki Kimura , Songyan Jiang , Kiyonari Harada , Yoko Yamashita , Hitoshi Ashida
      Drugs, xenobiotics including environmental pollutants, and certain food components modulate expression of drug-metabolizing enzymes. An aryl hydrocarbon receptor (AhR) possesses possible expression of phase I and phase II enzymes directly by binding of its ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and indirectly by regulating expression of nuclear factor-erythroid-2-related factor 2 (Nrf2). Previous our result demonstrated that luteolin, a natural flavonoid existing in vegetables and herbs, competed the binding of TCDD to AhR. In the present study, we investigated the effect of luteolin on the expression of drug-metabolizing enzymes through the AhR and Nrf2 pathways. Luteolin inhibited TCDD-induced protein expression of phase I enzyme cytochrome P450 1A1 (CYP1A1), phase II enzymes NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutathione-S-transferase P1 (GSTP1) in HepG2, Hepa1c1c7 and RL-34 cells in a dose-dependent manner. Luteolin suppressed TCDD- and tert-butylhydroquinone-induced Nrf2 protein by decreasing its stability in HepG2 cells. In tert-butylhydroquinone treated cells, luteolin dose-dependently inhibited NQO1, GSTP1 and aldo–keto reductases (AKRs). Of these, protein expression of CYP1A1 and GSTP1 was mainly dominated by the AhR pathway, while that of NQO1 and AKRs was by the Nrf2 pathway. In conclusion, luteolin inhibits expression of phase I and phase II drug-metabolizing enzymes by modulating the AhR and Nrf2 pathways.


      PubDate: 2014-07-26T20:02:45Z
       
  • Antioxidants and Redox Processes in Health – Bilateral Meeting
           Brazil-Japan
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Sayuri Miyamoto , Junji Terao



      PubDate: 2014-07-26T20:02:45Z
       
  • Dose-dependent functionality and toxicity of green tea polyphenols in
           experimental rodents
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Akira Murakami
      A large number of physiologically functional foods are comprised of plant polyphenols. Their antioxidative activities have been intensively studied for a long period and proposed to be one of the major mechanisms of action accounting for their health promotional and disease preventive effects. Green tea polyphenols (GTPs) are considered to possess marked anti-oxidative properties and versatile beneficial functions, including anti-inflammation and cancer prevention. On the other hand, some investigators, including us, have uncovered their toxicity at high doses presumably due to pro-oxidative properties. For instance, both experimental animal studies and epidemiological surveys have demonstrated that GTPs may cause hepatotoxicity. We also recently showed that diets containing high doses (0.5-1%) of a GTP deteriorated dextran sodium sulfate (DSS)-induced intestinal inflammation and carcinogenesis. In addition, colitis mode mice fed a 1% GTP exhibited symptoms of nephrotoxicity, as indicated by marked elevation of serum creatinine level. This diet also increased thiobarbituric acid-reactive substances, a reliable marker of oxidative damage, in both kidneys and livers even in normal mice, while the expression levels of antioxidant enzymes and heat shock proteins (HSPs) were diminished in colitis and normal mice. Intriguingly, GTPs at 0.01% and 0.1% showed hepato-protective activities, i.e., they significantly suppressed DSS-increased serum aspartate aminotransferase and alanine aminotransferase levels. Moreover, those diets remarkably restored DSS-down-regulated expressions of heme oxygenase-1 and HSP70 in livers and kidneys. Taken together, while low and medium doses of GTPs are beneficial in colitis model mice, unwanted side-effects occasionally emerge with high doses. This dose-dependent functionality and toxicity of GTPs are in accordance with the concept of hormesis, in which mild, but not severe, stress activates defense systems for adaptation and survival.
      Graphical abstract image Highlights

      PubDate: 2014-07-26T20:02:45Z
       
  • Quercetin-3-O-glucuronide inhibits noradrenaline-promoted invasion of
           MDA-MB-231 human breast cancer cells by blocking β2-adrenergic
           signaling
    • Abstract: Publication date: 1 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 557
      Author(s): Shunsuke Yamazaki , Noriyuki Miyoshi , Kyuichi Kawabata , Michiko Yasuda , Kayoko Shimoi
      Endogenous catecholamines such as adrenaline (A) and noradrenaline (NA) are released from the adrenal gland and sympathetic nervous system during exposure to stress. The adrenergic system plays a central role in stress signaling, and excessive stress was found to be associated with increased production of reactive oxygen species (ROS). Overproduction of ROS induces oxidative damage in tissues and causes the development of diseases such as cancer. In this study, we investigated the effects of quercetin-3-O-glucuronide (Q3G), a circulating metabolite of quercetin, which is a type of natural flavonoid, on the catecholamine-induced β2-adrenergic receptor (β2-AR)-mediated response in MDA-MB-231 human breast cancer cells expressing β2-AR. Treatment with A or NA at concentrations above 1μM generated significant levels of ROS, and NA treatment induced the gene expression of heme oxygenase-1 (HMOX1), and matrix metalloproteinase-2 (MMP-2) and -9 (MMP9). Inhibitors of p38 MAP kinase (SB203580), cAMP-dependent protein kinase (PKA) (H-89), activator protein-1 (AP-1) transcription factor (SR11302), and NF-κB and AP-1 (Tanshinone IIA) decreased MMP2 and MMP9 gene expression. NA also enhanced cAMP induction, RAS activation and phosphorylation of ERK1/2. These results suggested that the cAMP-PKA, MAPK, and ROS-NF-κB pathways are involved in β2-AR signaling. Treatment with 0.1μM Q3G suppressed ROS generation, cAMP and RAS activation, phosphorylation of ERK1/2 and the expression of HMOX1, MMP2, and MMP9 genes. Furthermore, Q3G (0.1μM) suppressed invasion of MDA-MB-231 breast cancer cells and MMP-9 induction, and inhibited the binding of [3H]-NA to β2-AR. These results suggest that Q3G may function to suppress invasion of breast cancer cells by controlling β2-adrenergic signaling, and may be a dietary chemopreventive factor for stress-related breast cancer.
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      PubDate: 2014-07-26T20:02:45Z
       
  • NMR study of the Z-DNA binding mode and B–Z transition activity of
           the Zα domain of human ADAR1 when perturbed by mutation on the
           α3 helix and β-hairpin
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Minjee Jeong , Ae-Ree Lee , Hee-Eun Kim , Yong-Geun Choi , Byong-Seok Choi , Joon-Hwa Lee
      The Zα domains of human ADAR1 (ZαADAR1) bind to Z-DNA via interaction mediated by the α3-core and β-hairpin. Five residues in the α3 helix and four residues in the β-hairpin play important roles in Zα function, forming direct or water-mediated hydrogen bonds with DNA backbone phosphates or interacting hydrophobically with DNA bases. To understand the roles of these residues during B–Z transition of duplex DNA, we performed NMR experiments on complexes of various ZαADAR1 mutants with a 6-bp DNA duplex at various protein-to-DNA molar ratios. Our study suggests that single mutations at residues K169, N173, or Y177 cause unusual conformational changes in the hydrophobic faces of helices α1, α2, and α3, which dramatically decrease the Z-DNA binding affinity. 1D imino proton spectra and chemical shift perturbation showed that single mutations at residues K170, R174, T191, P192, P193, or W195 slightly affected the Z-DNA binding affinity. A hydrogen exchange study proved that the K170A- and R174A-ZαADAR1 proteins could efficiently change B-DNA to left-handed Z-DNA via an active B–Z transition pathway, whereas the G2·C5 base pair was significantly destabilized compared to wild-type ZαADAR1.


      PubDate: 2014-07-26T20:02:45Z
       
  • NMR spectroscopy reveals a preferred conformation with a defined
           hydrophobic cluster for polyglutamine binding peptide 1
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Francisco Ramos-Martín , Rubén Hervás , Mariano Carrión-Vázquez , Douglas V. Laurents
      Several important human inherited neurodegenerative diseases are caused by “polyQ expansions”, which are aberrant long repeats of glutamine residues in proteins. PolyQ binding peptide 1 (QBP1), whose minimal active core sequence is Trp-Lys-Trp-Trp-Pro-Gly-Ile-Phe, binds to expanded polyQs and blocks their β-structure transition, aggregation and in vivo neurodegeneration. Whereas QBP1 is a widely used, commercially available product, its structure is unknown. Here, we have characterized the conformations of QBP1 and a scrambled peptide (Trp-Pro-Ile-Trp-Lys-Gly-Trp-Phe) in aqueous solution by CD, fluorescence and NMR spectroscopies. A CD maximum at 227nm suggests the presence of rigid Trp side chains in QBP1. Based on 41 NOE-derived distance constraints, the 3D structure of QBP1 was determined. The side chains of Trp 4 and Ile 7, and to a lesser extent, those of Lys 2, Trp 3 and Phe 8, form a small hydrophobic cluster. Pro 5 and Gly 6 adopt a type II tight turn and Lys 2’s ζ-NH3 + is positioned to form a favorable cation–π interaction with Trp 4’s indole ring. In contrast, the scrambled QBP1 peptide, which lacks inhibitory activity, does not adopt a preferred structure. These results provide a basis for future structure-based design approaches to further optimize QBP1 for therapy.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Agaricus meleagris pyranose dehydrogenase: Influence of covalent FAD
           linkage on catalysis and stability
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Iris Krondorfer , Dagmar Brugger , Regina Paukner , Stefan Scheiblbrandner , Katharina F. Pirker , Stefan Hofbauer , Paul G. Furtmüller , Christian Obinger , Dietmar Haltrich , Clemens K. Peterbauer
      Pyranose dehydrogenase (PDH) is a monomeric flavoprotein belonging to the glucose–methanol–choline (GMC) family of oxidoreductases. It catalyzes the oxidation of free, non-phosphorylated sugars to the corresponding keto sugars. The enzyme harbors an FAD cofactor that is covalently attached to histidine 103 via an 8α-N(3) histidyl linkage. Our previous work showed that variant H103Y was still able to bind FAD (non-covalently) and perform catalysis but steady-state kinetic parameters for several substrates were negatively affected. In order to investigate the impact of the covalent FAD attachment in Agaricus meleagris PDH in more detail, pre-steady-state kinetics, reduction potential and stability of the variant H103Y in comparison to the wild-type enzyme were probed. Stopped-flow analysis revealed that the mutation slowed down the reductive half-reaction by around three orders of magnitude whereas the oxidative half-reaction was affected only to a minor degree. This was reflected by a decrease in the standard reduction potential of variant H103Y compared to the wild-type protein. The existence of an anionic semiquinone radical in the resting state of both the wild-type and variant H103Y was demonstrated using electron paramagnetic resonance (EPR) spectroscopy and suggested a higher mobility of the cofactor in the variant H103Y. Unfolding studies showed significant negative effects of the disruption of the covalent bond on thermal and conformational stability. The results are discussed with respect to the role of covalently bound FAD in catalysis and stability.


      PubDate: 2014-07-26T20:02:45Z
       
  • Shifting redox states of the iron center partitions CDO between crosslink
           formation or cysteine oxidation
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Catherine W. Njeri , Holly R. Ellis
      Cysteine dioxygenase (CDO) is a mononuclear iron-dependent enzyme that catalyzes the oxidation of l-cysteine to l-cysteine sulfinic acid. The mammalian CDO enzymes contain a thioether crosslink between Cys93 and Tyr157, and purified recombinant CDO exists as a mixture of the crosslinked and non crosslinked isoforms. The current study presents a method of expressing homogenously non crosslinked CDO using a cell permeative metal chelator in order to provide a comprehensive investigation of the non crosslinked and crosslinked isoforms. Electron paramagnetic resonance analysis of purified non crosslinked CDO revealed that the iron was in the EPR silent Fe(II) form. Activity of non crosslinked CDO monitoring dioxygen utilization showed a distinct lag phase, which correlated with crosslink formation. Generation of homogenously crosslinked CDO resulted in an ∼5-fold higher k cat/K m value compared to the enzyme with a heterogenous mixture of crosslinked and non crosslinked CDO isoforms. EPR analysis of homogenously crosslinked CDO revealed that this isoform exists in the Fe(III) form. These studies present a new perspective on the redox properties of the active site iron and demonstrate that a redox switch commits CDO towards either formation of the Cys93–Tyr157 crosslink or oxidation of the cysteine substrate.


      PubDate: 2014-07-26T20:02:45Z
       
  • AMPK inhibits cardiac hypertrophy by promoting autophagy via mTORC1
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Yanh Li , Cong Chen , Fengj Yao , Qiao Su , Dan Liu , Ruic Xue , Gang Dai , Rong Fang , Juny Zeng , Yil Chen , Huil Huang , Yued Ma , Wenw Li , Lil Zhang , Chen Liu , Yug Dong
      AMPK, a serine/threonine protein kinase, has proven to be an important positive regulator of autophagy, which is a key factor in the regulation of cardiac hypertrophy. Thus, we explored whether AMPK could inhibit cardiac hypertrophy by regulating autophagy. In pressure overload induced cardiac hypertrophy, decreased autophagy was detected. Administration of AMPK activators (AICAR and metformin) significantly blocked hypertrophy, accompanied by enhanced autophagy level in the hearts. Furthermore, AMPK activation resulted in enhanced autophagosome formation and unimpaired lysosomal function. In vitro studies demonstrated adenoviral overexpression of constitutively activated AMPK increased autophagy and blunted PE-induced cardiomyocyte hypertrophy. Additionally, we found AICAR reduced the phosphorylation of the mTORC1 downstream effectors 4EBP1 and p70S6K, but AKT, which is a downstream signal of mTORC2, was not affected. Furthermore, activation by AMPK failed to lead to an additive effect on autophagy induced by the mTORC1 inhibitor rapamycin, indicating AMPK activates autophagy through the inhibition of mTORC1 but not of mTORC2. This study proved that AMPK can inhibit cardiac hypertrophy by stimulating autophagy through mTORC1 signaling.


      PubDate: 2014-07-26T20:02:45Z
       
  • Carbenoxolone induces permeability transition pore opening in rat
           mitochondria via the translocator protein TSPO and connexin43
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Tamara Azarashvili , Yulia Baburina , Dmitry Grachev , Olga Krestinina , Vassilios Papadopoulos , John J. Lemasters , Irina Odinokova , Georg Reiser
      Ca2+-induced permeability transition pore (mPTP) opening in isolated rat brain mitochondria is promoted through targeting of connexin43. After a threshold Ca2+ load, mitochondrial membrane potential drops and efflux of accumulated Ca2+ from the mitochondrial matrix occurs, indicating the mPTP opening. Specific antibodies were used to assess the role of the translocator protein (18kDa; TSPO) and connexin43 in swelling of isolated rat liver and brain mitochondria induced by carbenoxolone and the endogenous TSPO ligand protoporphyrin IX. Mitochondrial membrane potential, Ca2+ transport and oxygen consumption were determined using selective electrodes. All the parameters were detected simultaneously in a chamber with the selective electrodes. The phosphorylation state of mitochondrial protein targets was assessed. We report that Ca2+-induced mitochondrial swelling was strengthened in the presence of both carbenoxolone and protoporphyrin IX. The carbenoxolone- and protoporphyrin IX-accelerated mPTP induction in brain mitochondria was completely prevented by antibodies specific for the mitochondrial translocator protein (TSPO). The anti-TSPO antibodies were more effective than anti-сonnexin43 antibodies. Moreover, carbenoxolone-stimulated phosphorylation of mitochondrial proteins was inhibited by anti-TSPO antibodies. Taken together, the data suggests that, in addition to acting via connexion43, carbenoxolone may exert its effect on mPTP via mitochondrial outer membrane TSPO.


      PubDate: 2014-07-26T20:02:45Z
       
  • Insulin-like modulation of Akt/FoxO signaling by copper ions is
           independent of insulin receptor
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Ingrit Hamann , Kerstin Petroll , Larson Grimm , Andrea Hartwig , Lars-Oliver Klotz
      Copper ions are known to induce insulin-like effects in various cell lines, stimulating the phosphoinositide 3′-kinase (PI3K)/Akt signaling cascade and leading to the phosphorylation of downstream targets, including FoxO transcription factors. The aim of this work was to study the role of insulin- and IGF1-receptors (IR and IGF1R) in insulin-like signaling induced by copper in HepG2 human hepatoma cells. Cells were exposed to Cu(II) at various concentrations for up to 60min. While Akt and FoxO1a/FoxO3a were strongly phosphorylated in copper- and insulin-treated cells at all time points studied, only faint tyrosine phosphorylation of IR/IGF1R was detected in cells exposed to Cu(II) by either immunoprecipitation/immunoblot or by immunoblotting using phospho-specific antibodies, whereas insulin triggered strong phosphorylation at these sites. Pharmacological inhibition of IR/IGF1R modestly attenuated Cu-induced Akt and FoxO phosphorylation, whereas no attenuation of Cu-induced Akt activation was achieved by siRNA-mediated IR depletion. Cu(II)-induced FoxO1a nuclear exclusion was only slightly impaired by pharmacological inhibition of IR/IGF1R, whereas insulin-induced effects were blunted. In contrast, genistein, a broad-spectrum tyrosine kinase inhibitor, at concentrations not affecting IR/IGF1R, attenuated Cu(II)-induced Akt phosphorylation, pointing to the requirement of tyrosine kinases other than IR/IGF1R for Cu(II)-induced signaling.


      PubDate: 2014-07-26T20:02:45Z
       
  • ATM–p53 pathway causes G2/M arrest, but represses apoptosis in
           pseudolaric acid B-treated HeLa cells
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Guodong Yao , Min Qi , Xiaoling Ji , Simiao Fan , Lei Xu , Toshihiko Hayashi , Shin-ichi Tashiro , Satoshi Onodera , Takashi Ikejima
      Pseudolaric acid B (PAB) is a diterpene acid, isolated from the root and trunk bark of Pseudolarix kaempferi Gordon (Pinaceae). Previous studies demonstrated that PAB induced G2/M arrest and apoptosis in several cancer cell lines, but the relationship between G2/M arrest and apoptosis is still unclear. We examined the relevant signaling pathways for human cervical carcinoma HeLa cells treated with 1μM PAB. Intriguingly, we found that activation of ATM–p53 signaling pathway by the treatment with 1μM PAB played a protective role for the subsequent apoptosis. Although the treatment with 1μM PAB up-regulated the expression of cyclin B1 and p-Histone 3 (mitotic markers) at 12h, the expression decreased at 24 and 36h along with the up-down expression of mitotic markers. The expressions of p-ATM and p-p53 that were involved in G2/M arrest increased at 12h after treatment with PAB. However, a prolonged treatment with PAB (longer than 24h) caused cell apoptosis. When the cells were arrested in G1 or S phase by the treatment with serum starvation, cytosine β-d-arabinofuranoside (Ara-C) or hydroxyurea (Hu), the apoptotic ratio induced by PAB decreased.
      Graphical abstract image

      PubDate: 2014-07-26T20:02:45Z
       
  • Endothelium-derived nitric oxide (NO) activates the NO-epidermal growth
           factor receptor-mediated signaling pathway in bradykinin-stimulated
           angiogenesis
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Miriam S. Moraes , Paulo E. Costa , Wagner L. Batista , Taysa Paschoalin , Marli F. Curcio , Roberta E. Borges , Murched O. Taha , Fábio V. Fonseca , Arnold Stern , Hugo P. Monteiro
      Nitric oxide (NO) is involved in angiogenesis and stimulates the EGF-R signaling pathway. Stimulation of different endothelial cell lines with bradykinin (BK) activates the endothelial NO synthase (eNOS) and promotes EGF-R tyrosine phosphorylation. Increase in NO production correlated with enhanced phosphorylation of tyrosine residues and S-nitrosylation of the EGF-R. NO-mediated stimulatory effects on tyrosine phosphorylation of the EGF-R, where cGMP independent. Inhibition of soluble guanylyl cyclase followed by BK stimulation of human umbilical vein endothelial cells (HUVECs) did not change tyrosine phosphorylation levels of EGF-R. BK-stimulation of HUVEC promoted S-nitrosylation of the phosphatase SHP-1 and of p21Ras. Phosphorylation and activation of the ERK1/2 MAP kinases mediated by BK was dependent on the activation of the B2 receptor, of the EGF-R, and of p21 Ras. Inhibition of BK-stimulated S-nitrosylation prevented the activation of the ERK1/2 MAP kinases. Furthermore, activated ERK1/2 MAP kinases inhibited internalization of EGF-R by phosphorylating specific Thr residues of its cytoplasmic domain. BK-induced proliferation of endothelial cells was partially inhibited by the NOS inhibitor (L-NAME) and by the MEK inhibitor (PD98059). BK stimulated the expression of vascular endothelial growth factor (VEGF). VEGF expression was dependent on the activation of the EGF-R, the B2 receptor, p21Ras, and on NO generation. A Matrigel®-based in vitro assay for angiogenesis showed that BK induced the formation of capillary-like structures in HUVEC, but not in those cells expressing a mutant of the EGF-R lacking tyrosine kinase activity. Additionally, pre-treatment of BK-stimulated HUVEC with L-NAME, PD98059, and with SU5416, a specific inhibitor of VEGFR resulted in inhibition of in vitro angiogenesis. Our findings indicate that BK-mediated angiogenesis in endothelial cells involves the induction of the expression of VEGF associated with the activation of the NO/EGF-R/p21Ras/ERK1/2 MAP kinases signaling pathway.


      PubDate: 2014-07-26T20:02:45Z
       
  • 14-3-3ζ regulates nuclear trafficking of protein phosphatase 1α
           (PP1α) in HEK-293 cells
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Myrka Jérôme , Hemant K. Paudel
      Protein phosphatase 1 (PP1) is one of the major Ser/Thr phosphatases in mammalian cells. There are four isoforms of PP1 namely, PP1α, PP1β/δ, PP1γ1 and PP1γ2. PP1γ and PP1β translocate to the nucleus by binding to a co-transporter that contains a nuclear localization signal. The mechanism by which PP1α shuttles between the nucleus and the cytosol is not known. In this study, we found that PP1α co-immunoprecipitates with 14-3-3ζ from HEK-293 cell lysates. By co-immunoprecipitation and GST pull-down assay, we determined that 14-3-3ζ binds to both PP1α (WT) and PP1α (T320A), and that phosphorylation of PP1α is not required for binding. Using PP1α deletion mutants, we located the 14-3-3ζ binding region within PP1α residues 159–279. An in vitro assay showed that 14-3-3ζ does not affect PP1α activity. When HEK-293 cells expressing PP1α and 14-3-3ζ were subjected to subcellular fractionation, the ratio of cytosolic vs. nuclear PP1α was significantly higher in cells expressing PP1α and 14-3-3ζ than those expressing PP1α alone. In cells expressing a dominant negative 14-3-3ζ (K49E), PP1α accumulated in the nucleus. Our results show that 14-3-3ζ binds to PP1α and causes its retention in the cytosol which suggests that 14-3-3ζ regulates nuclear trafficking of PP1α in mammalian cells.


      PubDate: 2014-07-26T20:02:45Z
       
  • Mechanisms of axon regeneration and its inhibition: Roles of sulfated
           glycans
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Kenji Kadomatsu , Kazuma Sakamoto
      Axons in the peripheral nervous system can regenerate after injury, whereas axons in the central nervous system (CNS) do not readily regenerate. Intrinsic regenerating capacity and emerging inhibitors could explain these contrasting phenotypes. Among the inhibitors, sulfated sugar chains including chondroitin sulfate and keratan sulfate have recently attracted attention, since these sugar chains strongly inhibit axon regeneration and also induce dystrophic endball formation, a hallmark of injured axons in the adult mammalian CNS. In addition, chondroitin sulfate is a negative regulator of synaptic plasticity. To overcome the inability of CNS axons to regenerate, a comprehensive understanding of both the positive and negative regulations of axon regeneration is required. These may include signaling waves from the injury site to the nucleus, intracellular signals for growth cone formation and axon regeneration, intracellular signals for the inhibition of axon regeneration, and extracellular inhibitory signals and their receptors. This review addresses these issues, with a focus on the roles of chondroitin sulfate and keratan sulfate.


      PubDate: 2014-07-26T20:02:45Z
       
  • The Great Beauty of the osteoclast
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Alfredo Cappariello , Antonio Maurizi , Vimal Veeriah , Anna Teti
      Much has been written recently on osteoclast biology, but this cell type still astonishes scientists with its multifaceted functions and unique properties. The last three decades have seen a change in thinking about the osteoclast, from a cell with a single function, which just destroys the tissue it belongs to, to an “orchestrator” implicated in the concerted regulation of bone turnover. Osteoclasts have unique morphological features, organelle distribution and plasma membrane domain organization. They require polarization to cause extracellular bone breakdown and release of the digested bone matrix products into the circulation. Osteoclasts contribute to the control of skeletal growth and renewal. Alongside other organs, including kidney, gut, thyroid and parathyroid glands, they also affect calcemia and phosphatemia. Osteoclasts are very sensitive to pro-inflammatory stimuli, and studies in the ‘00s ascertained their tight link with the immune system, bringing about the question why bone needs a cell regulated by the immune system to remove the extracellular matrix components. Recently, osteoclasts have been demonstrated to contribute to the hematopoietic stem cell niche, controlling local calcium concentration and regulating the turnover of factors essential for hematopoietic stem cell mobilization. Finally, osteoclasts are important regulators of osteoblast activity and angiogenesis, both by releasing factors stored in the bone matrix, and secreting “clastokines” that regulate the activity of neighboring cells. All these facets will be discussed in this review article, with the aim of underscoring The Great Beauty of the osteoclast.


      PubDate: 2014-07-26T20:02:45Z
       
  • Expression and induction of small heat shock proteins in rat heart under
           chronic hyperglycemic conditions
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): V. Sudhakar Reddy , Ch. Uday Kumar , G. Raghu , G. Bhanuprakash Reddy
      The induction of small heat shock proteins (sHsp) is observed under various stress conditions to protect the cells and organisms from adverse events including diabetes. Diabetic cardiomyopathy is a common complication of diabetes. Therefore, in this study, we investigated the expression of sHsp under chronic hyperglycemic conditions in rat heart. Hyperglycemia was induced in WNIN rats by intraperitoneal injection of streptozotocin and maintained for a period of 12weeks. Expression of sHsp, phosphorylation and translocation of phosphoforms of Hsp27 and αB-crystallin (αBC) from cytosolic fraction to cytoskeletal fraction was analyzed. While the expression of MKBP, HspB3, αBC was found to be increased in diabetic heart, expression of Hsp20 was decreased. Chronic hyperglycemia further induced phosphorylation of αBC at S59, S45, Hsp27 at S82, p38MAPK and p44/42MAPK. However, pS59-αBC and pS82-Hsp27 were translocated from detergent-soluble to detergent-insoluble fraction under hyperglycemic conditions. Furthermore, the interaction of pS82-Hsp27 and pS59-αBC with desmin was increased under hyperglycemia. However, the interaction of αBC and pS59-αBC with Bax was impaired by chronic hyperglycemia. These results suggest up regulation of sHsp (MKBP, HspB3 and αBC), phosphorylation and translocation of Hsp27 and αBC to striated sarcomeres and impaired interaction of αBC and pS59-αBC with Bax under chronic hyperglycemia.


      PubDate: 2014-07-26T20:02:45Z
       
  • Neurogenins in brain development and disease: An overview
    • Abstract: Publication date: 15 September 2014
      Source:Archives of Biochemistry and Biophysics, Volume 558
      Author(s): Liqun Yuan , Bassem A. Hassan
      The production of neurons, astrocytes and oligodendrocytes is regulated by a group of transcription factors, which determine cell fates and specify subtype identities in the nervous system. Here we focus on profiling the distinct roles of Neurogenin (Ngn or Neurog) family members during the neuronal development. Ngn proteins are tightly regulated to be expressed at defined times and positions of different progenitor cell pools. In addition to their well-elucidated proneural function, Ngn proteins play various critical roles to specify or maintain cell fate and regulate neurite outgrowth and targeting in the central nervous system. Finally, Ngns have been associated with neuronal disorders. Therefore understanding the function and regulation of Ngns will not only improve the understanding of the molecular mechanism underlying the development of nervous system, but may also provide insight into neuronal disease.


      PubDate: 2014-07-26T20:02:45Z
       
  • Effects of the melanin precursor 5,6-dihydroxy-indole-2-carboxylic acid
           (DHICA) on DNA damage and repair in the presence of reactive oxygen
           species
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Maria Carolina Pellosi , Andréia Akemi Suzukawa , Alexsandra Cristina Scalfo , Paolo Di Mascio , Carolina Parga Martins Pereira , Nadja Cristhina de Souza Pinto , Daniela de Luna Martins , Glaucia Regina Martinez
      Eumelanin is a heterogeneous polymer composed of 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI). Studies have shown that DHICA promotes single strand breaks in plasmid DNA exposed to ultraviolet B radiation (UVB, 313nm) and in DNA from human keratinocytes exposed to ultraviolet A radiation (UVA, 340–400nm). Singlet molecular oxygen (1O2) is the main reactive species formed by UVA radiation on the skin. In this context, we now report that DHICA can cause single strand breaks in plasmid DNA even in the absence of light radiation. Interestingly, when DHICA was pre-oxidized by 1O2, it lost this harmful capacity. It was also found that DHICA could interact with DNA, disturbing Fpg activity and decreasing its recognition of lesions by ∼50%. Additionally, the free nucleoside deoxyguanosine (dGuo) was used to evaluate whether DHICA would interfere with the formation of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodGuo) and spiroiminodihydantoin (dSp) by 1O2 or with the formation of 8-oxodGuo by hydroxyl radical ( OH). We observed that when dGuo was oxidized by 1O2 in the presence of DHICA, 8-oxodGuo formation was increased. However, when dGuo was oxidized by OH in the presence of DHICA, 8-oxodGuo levels were lower than in the absence of the precursor. Overall, our data reveal an important role for this eumelanin precursor in both the promotion and the protection of DNA damage and imply that it can impair DNA repair.


      PubDate: 2014-06-07T15:27:45Z
       
  • Specific localization of quercetin-3-O-glucuronide in human brain
    • Abstract: Publication date: Available online 1 June 2014
      Source:Archives of Biochemistry and Biophysics
      Author(s): Akari Ishisaka , Rie Mukai , Junji Terao , Noriyuki Shibata , Yoshichika Kawai
      In recent years, many papers have suggested that dietary flavonoids may exert beneficial effects in the brain tissue for the protection of neurons against oxidative stress and inflammation. However, the bioavailability of flavonoids across the blood–brain barrier and the localization in the brain remain controversial. Thus, we examined the localization of quercetin-3-O-glucuronide (Q3GA), a major phase-II metabolite of quercetin, in the human brain tissues with or without cerebral infarction by immunohistochemical staining using anti-Q3GA antibody. A significant immunoreactivity was observed in the epithelial cells of the choroid plexus, which constitute the structural basis of the blood–cerebrospinal fluid (CSF) barrier, and in the foamy macrophages of recent infarcts. The cellular accumulation of Q3GA was also reproduced in vitro in macrophage-like RAW264, microglial MG6, and brain capillary endothelial RBEC1. It is of interest that a common feature of these cell lines is the deconjugation of Q3GA, resulting in the cellular accumulation of non-conjugated quercetin and the methylated forms. We then examined the anti-inflammatory activity of Q3GA and the deconjugated forms in the lipopolysaccharide-stimulated macrophage cells and revealed that the deconjugated forms (quercetin and a methylated form isorhamnetin), but not Q3GA itself, exhibited inhibitory effects on the inflammatory responses through attenuation of the c-Jun N-terminal kinase pathway. These results suggested that a quercetin glucuronide can pass through the blood–brain barrier, perhaps the CSF barrier, accumulate in specific types of cells, such as macrophages, and act as anti-inflammatory agents in the brain through deconjugation into the bioactive non-conjugated forms.


      PubDate: 2014-06-07T15:27:45Z
       
 
 
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