Subjects -> BIOLOGY (Total: 3447 journals)
    - BIOCHEMISTRY (267 journals)
    - BIOENGINEERING (143 journals)
    - BIOLOGY (1643 journals)
    - BIOPHYSICS (50 journals)
    - BIOTECHNOLOGY (269 journals)
    - BOTANY (250 journals)
    - CYTOLOGY AND HISTOLOGY (32 journals)
    - ENTOMOLOGY (75 journals)
    - GENETICS (171 journals)
    - MICROBIOLOGY (286 journals)
    - MICROSCOPY (12 journals)
    - ORNITHOLOGY (29 journals)
    - PHYSIOLOGY (73 journals)
    - ZOOLOGY (147 journals)

BIOLOGY (1643 journals)                  1 2 3 4 5 6 7 8 | Last

Showing 1 - 200 of 1720 Journals sorted alphabetically
AAPS Journal     Hybrid Journal   (Followers: 30)
Achievements in the Life Sciences     Open Access   (Followers: 8)
ACS Pharmacology & Translational Science     Hybrid Journal   (Followers: 2)
ACS Synthetic Biology     Hybrid Journal   (Followers: 31)
Acta Biologica Colombiana     Open Access   (Followers: 7)
Acta Biologica Hungarica     Full-text available via subscription   (Followers: 5)
Acta Biologica Sibirica     Open Access   (Followers: 2)
Acta Biologica Turcica     Open Access   (Followers: 1)
Acta Biologica Venezuelica     Open Access  
Acta Biomaterialia     Hybrid Journal   (Followers: 30)
Acta Biotheoretica     Hybrid Journal   (Followers: 3)
Acta Chiropterologica     Full-text available via subscription   (Followers: 6)
acta ethologica     Hybrid Journal   (Followers: 4)
Acta Fytotechnica et Zootechnica     Open Access   (Followers: 1)
Acta Limnologica Brasiliensia     Open Access   (Followers: 4)
Acta Médica Costarricense     Open Access   (Followers: 2)
Acta Musei Silesiae, Scientiae Naturales     Open Access   (Followers: 1)
Acta Neurobiologiae Experimentalis     Open Access  
Acta Parasitologica     Hybrid Journal   (Followers: 12)
Acta Scientiae Biological Research     Open Access   (Followers: 1)
Acta Scientiarum. Biological Sciences     Open Access   (Followers: 2)
Acta Scientifica Naturalis     Open Access   (Followers: 3)
Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis     Open Access   (Followers: 1)
Actualidades Biológicas     Open Access   (Followers: 1)
Advanced Biosystems     Hybrid Journal  
Advanced Health Care Technologies     Open Access   (Followers: 10)
Advanced Journal of Graduate Research     Open Access   (Followers: 1)
Advanced Nonlinear Studies     Hybrid Journal  
Advanced Quantum Technologies     Hybrid Journal  
Advanced Studies in Biology     Open Access   (Followers: 1)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Bioinformatics     Open Access   (Followers: 20)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4)
Advances in Biology     Open Access   (Followers: 12)
Advances in Cell Biology/ Medical Journal of Cell Biology     Open Access   (Followers: 30)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 14)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Ecological Research     Full-text available via subscription   (Followers: 44)
Advances in Environmental Sciences - International Journal of the Bioflux Society     Open Access   (Followers: 19)
Advances in Enzyme Research     Open Access   (Followers: 11)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 9)
Advances in Genome Biology     Full-text available via subscription   (Followers: 11)
Advances in High Energy Physics     Open Access   (Followers: 22)
Advances in Human Biology     Open Access   (Followers: 5)
Advances in Life Science and Technology     Open Access   (Followers: 20)
Advances in Life Sciences     Open Access   (Followers: 7)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 26)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 7)
Advances in Structural Biology     Full-text available via subscription   (Followers: 6)
Advances in Tropical Biodiversity and Environmental Sciences     Open Access   (Followers: 3)
Advances in Virus Research     Full-text available via subscription   (Followers: 6)
Adversity and Resilience Science : Journal of Research and Practice     Hybrid Journal   (Followers: 1)
African Journal of Range & Forage Science     Hybrid Journal   (Followers: 12)
AFRREV STECH : An International Journal of Science and Technology     Open Access   (Followers: 3)
Ageing Research Reviews     Hybrid Journal   (Followers: 12)
Aging Cell     Open Access   (Followers: 26)
Agrokémia és Talajtan     Full-text available via subscription   (Followers: 2)
Agrokreatif Jurnal Ilmiah Pengabdian kepada Masyarakat     Open Access  
AJP Cell Physiology     Hybrid Journal   (Followers: 18)
AJP Endocrinology and Metabolism     Hybrid Journal   (Followers: 25)
AJP Lung Cellular and Molecular Physiology     Hybrid Journal   (Followers: 3)
Al-Kauniyah : Jurnal Biologi     Open Access  
Alasbimn Journal     Open Access   (Followers: 2)
Alces : A Journal Devoted to the Biology and Management of Moose     Open Access  
AMB Express     Open Access   (Followers: 1)
Ambix     Hybrid Journal   (Followers: 3)
American Biology Teacher     Full-text available via subscription   (Followers: 14)
American Fern Journal     Full-text available via subscription   (Followers: 1)
American Journal of Agricultural and Biological Sciences     Open Access   (Followers: 9)
American Journal of Bioethics     Hybrid Journal   (Followers: 16)
American Journal of Human Biology     Hybrid Journal   (Followers: 18)
American Journal of Medical and Biological Research     Open Access   (Followers: 10)
American Journal of Plant Sciences     Open Access   (Followers: 21)
American Journal of Primatology     Hybrid Journal   (Followers: 16)
American Malacological Bulletin     Full-text available via subscription   (Followers: 3)
American Naturalist     Full-text available via subscription   (Followers: 81)
Amphibia-Reptilia     Hybrid Journal   (Followers: 6)
Anadol University Journal of Science and Technology B : Theoritical Sciences     Open Access  
Anadolu University Journal of Science and Technology : C Life Sciences and Biotechnology     Open Access   (Followers: 2)
Anaerobe     Hybrid Journal   (Followers: 4)
Anales de Biología     Open Access   (Followers: 2)
Analytical Methods     Full-text available via subscription   (Followers: 13)
Anatomical Science International     Hybrid Journal   (Followers: 3)
Animal Cells and Systems     Hybrid Journal   (Followers: 5)
Animal Models and Experimental Medicine     Open Access  
Annales de Limnologie - International Journal of Limnology     Hybrid Journal   (Followers: 1)
Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale     Full-text available via subscription   (Followers: 3)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3)
Annales Universitatis Mariae Curie-Sklodowska, sectio C – Biologia     Open Access   (Followers: 1)
Annals of Applied Biology     Hybrid Journal   (Followers: 8)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 19)
Annals of Human Biology     Hybrid Journal   (Followers: 6)
Annals of Science and Technology     Open Access  
Annual Research & Review in Biology     Open Access   (Followers: 2)
Annual Review of Biomedical Engineering     Full-text available via subscription   (Followers: 15)
Annual Review of Biophysics     Full-text available via subscription   (Followers: 26)
Annual Review of Cancer Biology     Full-text available via subscription   (Followers: 4)
Annual Review of Cell and Developmental Biology     Full-text available via subscription   (Followers: 42)
Annual Review of Food Science and Technology     Full-text available via subscription   (Followers: 15)
Annual Review of Genomics and Human Genetics     Full-text available via subscription   (Followers: 27)
Annual Review of Phytopathology     Full-text available via subscription   (Followers: 13)
Anthropological Review     Open Access   (Followers: 24)
Antibiotics     Open Access   (Followers: 9)
Antioxidants     Open Access   (Followers: 5)
Antioxidants & Redox Signaling     Hybrid Journal   (Followers: 9)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5)
Anzeiger für Schädlingskunde     Hybrid Journal   (Followers: 1)
Apidologie     Hybrid Journal   (Followers: 5)
Apmis     Hybrid Journal   (Followers: 2)
APOPTOSIS     Hybrid Journal   (Followers: 9)
Applied Biology     Open Access   (Followers: 2)
Applied Bionics and Biomechanics     Open Access   (Followers: 7)
Applied Vegetation Science     Full-text available via subscription   (Followers: 10)
Aquaculture Environment Interactions     Open Access   (Followers: 4)
Aquaculture International     Hybrid Journal   (Followers: 26)
Aquaculture Reports     Open Access   (Followers: 3)
Aquaculture, Aquarium, Conservation & Legislation - International Journal of the Bioflux Society     Open Access   (Followers: 7)
Aquatic Biology     Open Access   (Followers: 8)
Aquatic Ecology     Hybrid Journal   (Followers: 38)
Aquatic Ecosystem Health & Management     Hybrid Journal   (Followers: 16)
Aquatic Science and Technology     Open Access   (Followers: 4)
Aquatic Toxicology     Hybrid Journal   (Followers: 24)
Archaea     Open Access   (Followers: 4)
Archiv für Molluskenkunde: International Journal of Malacology     Full-text available via subscription   (Followers: 3)
Archives of Biological Sciences     Open Access  
Archives of Microbiology     Hybrid Journal   (Followers: 10)
Archives of Natural History     Hybrid Journal   (Followers: 8)
Archives of Oral Biology     Hybrid Journal   (Followers: 3)
Archives of Virology     Hybrid Journal   (Followers: 5)
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2)
Arid Ecosystems     Hybrid Journal   (Followers: 3)
Arquivos do Instituto Biológico     Open Access   (Followers: 1)
Arquivos do Museu Dinâmico Interdisciplinar     Open Access  
Arthropod Structure & Development     Hybrid Journal   (Followers: 2)
Arthropods     Open Access   (Followers: 1)
Artificial DNA: PNA & XNA     Hybrid Journal   (Followers: 3)
Asian Bioethics Review     Full-text available via subscription   (Followers: 3)
Asian Journal of Biodiversity     Open Access   (Followers: 5)
Asian Journal of Biological Sciences     Open Access   (Followers: 3)
Asian Journal of Biology     Open Access   (Followers: 2)
Asian Journal of Biotechnology and Bioresource Technology     Open Access   (Followers: 1)
Asian Journal of Cell Biology     Open Access   (Followers: 6)
Asian Journal of Developmental Biology     Open Access   (Followers: 3)
Asian Journal of Medical and Biological Research     Open Access   (Followers: 5)
Asian Journal of Nematology     Open Access   (Followers: 4)
Asian Journal of Poultry Science     Open Access   (Followers: 5)
Atti della Accademia Peloritana dei Pericolanti - Classe di Scienze Medico-Biologiche     Open Access  
Australian Life Scientist     Full-text available via subscription   (Followers: 2)
Australian Mammalogy     Hybrid Journal   (Followers: 8)
Autophagy     Hybrid Journal   (Followers: 4)
Avian Biology Research     Full-text available via subscription   (Followers: 6)
Avian Conservation and Ecology     Open Access   (Followers: 15)
Bacterial Empire     Open Access   (Followers: 1)
Bacteriology Journal     Open Access   (Followers: 1)
Bacteriophage     Full-text available via subscription   (Followers: 3)
Bangladesh Journal of Bioethics     Open Access  
Bangladesh Journal of Plant Taxonomy     Open Access  
Bangladesh Journal of Scientific Research     Open Access   (Followers: 1)
Batman Üniversitesi Yaşam Bilimleri Dergisi     Open Access  
Berita Biologi     Open Access   (Followers: 1)
Between the Species     Open Access   (Followers: 1)
Bio Tribune Magazine     Hybrid Journal  
BIO Web of Conferences     Open Access  
BIO-Complexity     Open Access  
Bio-Grafía. Escritos sobre la Biología y su enseñanza     Open Access  
Bio-Lectura     Open Access  
BIO-SITE : Biologi dan Sains Terapan     Open Access   (Followers: 1)
Bioanalytical Reviews     Hybrid Journal   (Followers: 2)
Biocatalysis and Biotransformation     Hybrid Journal   (Followers: 6)
BioCentury Innovations     Full-text available via subscription   (Followers: 2)
Biochemistry and Cell Biology     Hybrid Journal   (Followers: 17)
Biochimie     Hybrid Journal   (Followers: 6)
BioControl     Hybrid Journal   (Followers: 6)
Biocontrol Science and Technology     Hybrid Journal   (Followers: 8)
Biodemography and Social Biology     Hybrid Journal  
BIODIK : Jurnal Ilmiah Pendidikan Biologi     Open Access   (Followers: 1)
BioDiscovery     Open Access   (Followers: 2)
Biodiversidade e Conservação Marinha : Revista CEPSUL     Open Access  
Biodiversitas : Journal of Biological Diversity     Open Access  
Biodiversity Data Journal     Open Access   (Followers: 4)
Biodiversity Informatics     Open Access   (Followers: 1)
Biodiversity Information Science and Standards     Open Access   (Followers: 2)
Biodiversity: Research and Conservation     Open Access   (Followers: 27)
Bioedukasi : Jurnal Pendidikan Biologi FKIP UM Metro     Open Access  
Bioeksperimen : Jurnal Penelitian Biologi     Open Access  
Bioelectrochemistry     Hybrid Journal   (Followers: 2)
Bioelectromagnetics     Hybrid Journal   (Followers: 2)
Bioenergy Research     Hybrid Journal   (Followers: 4)
Bioengineering and Bioscience     Open Access   (Followers: 3)
BioEssays     Hybrid Journal   (Followers: 11)
Bioethics     Hybrid Journal   (Followers: 18)
BioéthiqueOnline     Open Access  
Biofabrication     Hybrid Journal   (Followers: 5)
Biofilms     Full-text available via subscription   (Followers: 2)
Biogeosciences (BG)     Open Access   (Followers: 12)
Biogeosciences Discussions (BGD)     Open Access   (Followers: 3)

        1 2 3 4 5 6 7 8 | Last

Similar Journals
Journal Cover
Biochimie
Journal Prestige (SJR): 1.554
Citation Impact (citeScore): 3
Number of Followers: 6  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 0300-9084
Published by Elsevier Homepage  [3204 journals]
  • Unique functional properties of slow skeletal muscle tropomyosin
    • Abstract: Publication date: Available online 26 March 2020Source: BiochimieAuthor(s): Alexander M. Matyushenko, Daniil V. Shchepkin, Galina V. Kopylova, Sergey Y. Bershitsky, Dmitrii I. Levitsky
       
  • Protein–protein interactions of ER–resident selenoproteins with their
           physiological partners
    • Abstract: Publication date: Available online 15 March 2020Source: BiochimieAuthor(s): Varlamova Elena Gennadyevna
       
  • Structural analysis of the CARB β-lactamase from Vibrio parahaemolyticus
           facilitates application of the β-lactam/β-lactamase inhibitor therapy
    • Abstract: Publication date: Available online 13 March 2020Source: BiochimieAuthor(s): Peihai Li, Changshui Liu, Baojie Li, Qingjun Ma
       
  • Development and validation of a rapid, specific and sensitive LC-MS/MS
           bioanalytical method for eicosanoid quantification - assessment of
           arachidonic acid metabolic pathway activity in hypertensive rats
    • Abstract: Publication date: Available online 13 March 2020Source: BiochimieAuthor(s): Agnieszka Kij, Kamil Kus, Izabela Czyzynska-Cichon, Stefan Chlopicki, Maria Walczak
       
  • Upregulation of enzymatic antioxidants in CD4+ T cells of autistic
           children
    • Abstract: Publication date: Available online 12 March 2020Source: BiochimieAuthor(s): Ahmed Nadeem, Sheikh F. Ahmad, Naif O. Al-Harbi, Abdullah F. Alasmari, Laila Y. AL-Ayadhi, Fawaz Alasmari, Khalid E. Ibrahim, Sabry M. Attia, Saleh A. Bakheet
       
  • Truncation of Huia versabilis Bowman-Birk inhibitor increases its
           selectivity, matriptase-1 inhibitory activity and proteolytic stability
    • Abstract: Publication date: Available online 10 March 2020Source: BiochimieAuthor(s): Agata Gitlin-Domagalska, Dawid Dębowski, Katarzyna Gucwa, Dominika Starego, Natalia Ptaszyńska, Adam Sieradzan, Agnieszka Karczyńska, Sergey A. Samsonov, Martin Mangold, Michael Gütschow, Anna Łęgowska, Krzysztof Rolka
       
  • In vivo evidence that bezafibrate prevents oxidative stress and
           mitochondrial dysfunction caused by 3-methylglutaric acid in rat liver
    • Abstract: Publication date: Available online 10 March 2020Source: BiochimieAuthor(s): Nevton Teixeira da Rosa-Junior, Belisa Parmeggiani, Nícolas Manzke Glänzel, Leonardo de Moura Alvorcem, Marina Rocha Frusciante, Carlos Severo Dutra Filho, Moacir Wajner, Guilhian Leipnitz
       
  • Interaction Of 5-Substituted Pyrimidine Nucleoside Analogues And
           M.Tuberculosis: A View Through An Electron Microscope
    • Abstract: Publication date: Available online 6 March 2020Source: BiochimieAuthor(s): Anastasia L. Khandazhinskaya, Elena S. Matyugina, Liudmila A. Alexandrova, Vasiliy A. Kezin, Larisa N. Chernousova, Tatiana G. Smirnova, Sofya N. Andreevskaya, Vladimir I. Popenko, Olga G. Leonova, Sergey N. Kochetkov
       
  • Body mass index determines the response of plasma sulfur amino acids to
           methionine loading
    • Abstract: Publication date: Available online 5 March 2020Source: BiochimieAuthor(s): Amany K. Elshorbagy, Ian Graham, Helga Refsum
       
  • MksB, an alternate condensin from Mycobacterium smegmatis is involved in
           DNA binding and condensation
    • Abstract: Publication date: Available online 5 March 2020Source: BiochimieAuthor(s): Suchitra Pradhan, Swathy Velaparambil Bipinachandran, Pratibha Kumari, M. Suguna, M. Dharma Prasad, Ravi Kumar
       
  • Identification and characterization of dihydropyrimidinase inhibited by
           plumbagin isolated from Nepenthes miranda extract
    • Abstract: Publication date: Available online 5 March 2020Source: BiochimieAuthor(s): Yen-Hua Huang, Yi Lien, Jung-Hung Chen, En-Shyh Lin, Cheng-Yang Huang
       
  • In vitro and computational studies of natural products related to perezone
           as anti-neoplastic agents
    • Abstract: Publication date: Available online 5 March 2020Source: BiochimieAuthor(s): Maricarmen Hernández-Rodríguez, Pablo I. Mendoza Sánchez, Martha Edith Macías Perez, Erika Rosales Cruz, Elvia Mera Jiménez, Juan Manuel Aceves-Hernández, María Inés Nicolás-Vázquez, René Miranda Ruvalcaba
       
  • Exosomal Nrf2: from anti-oxidant and anti-inflammation response to wound
           healing and tissue regeneration in aged-related diseases
    • Abstract: Publication date: Available online 26 February 2020Source: BiochimieAuthor(s): Houman Kahroba, Yasamin Davatgaran-Taghipour
       
  • Molecular characterization of Ditylenchus destructor voltage-gated calcium
           channel α1 subunits and analysis of the effect of their knockdown on
           nematode activity
    • Abstract: Publication date: Available online 25 February 2020Source: BiochimieAuthor(s): Shan Ye, Rune Zeng, Jianyu Zhou, Mingwei An, Zhong Ding
       
  • Cytochrome 450 metabolites of arachidonic acid (20-HETE, 11,12-EET and
           14,15-EET) promote pheochromocytoma cell growth and tumor associated
           angiogenesis
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Colombero Cecilia, Cárdenas Sofía, Venara Marcela, Martin Ayelen, Pennisi Patricia, Barontini Marta, Nowicki Susana
       
  • Is the gut microbiota dysbiotic in patients with classical
           homocystinuria'
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Gustavo M. Rizowy, Soraia Poloni, Karina Colonetti, Karina C. Donis, Priscila T. Dobbler, Sandra Leistner-Segal, Luiz Fernando W. Roesch, Ida Vanessa D. Schwartz
       
  • Protein-protein interactions involving enzymes of the mammalian methionine
           and homocysteine metabolism
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Francisco Portillo, Jesús Vázquez, María A. Pajares
       
  • Deiminated Proteins and Extracellular Vesicles as Novel Biomarkers in
           Pinnipeds: Grey seal (Halichoerus gryptus) and Harbour seal (Phoca
           vitulina)
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Bergljót Magnadóttir, Pinar Uysal-Onganer, Igor Kraev, Vilhjálmur Svansson, Karl Skírnisson, Sigrun Lange
       
  • Analysis of RNA binding properties of human Ku protein reveals its
           interactions with 7SK snRNA and protein components of 7SK snRNP complex
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Olga Shadrina, Irina Garanina, Sergey Korolev, Timofei Zatsepin, Jeanne Van Assche, Fadoua Daouad, Clementine Wallet, Olivier Rohr, Marina Gottikh
       
  • Mechanisms of homocysteine-induced damage to the endothelial, medial and
           adventitial layers of the arterial wall
    • Abstract: Publication date: Available online 24 February 2020Source: BiochimieAuthor(s): Brittany Balint, Viola Kosgei Jepchumba, Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez
       
  • Inside front cover-EDB
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s):
       
  • Epigenetically silenced LINC02381 functions as a tumor suppressor by
           regulating PI3K-Akt signaling pathway
    • Abstract: Publication date: Available online 21 February 2020Source: BiochimieAuthor(s): Meisam Jafarzadeh, Bahram M. Soltani, Masoud Soleimani, Saman Hosseinkhani Recent advances have revealed that lncRNAs play important roles in tumorigenesis. However, only a small number of functional lncRNAs have been well characterized, particularly in colorectal cancer. Therefore, more extensive studies are needed to identify and characterize these lncRNAs to better understand cancer progression. In the present study, using available RNA-seq data, we found that LINC02381 (NR_026656.1) differentially expresses in CRC tissues compared to normal pairs. Consistently, RT-qPCR results showed that LINC02381 was down regulated in CRC tissues and also in different cancerous cell lines. CRC cells treatment with de-methylating and chemotherapy agents indicated that DNA methylation of LINC02381 may be responsible for the transcriptional silencing of LINC02381 in colorectal cancer cells. Then, the functional changes of the cells in response to LINC02381 alteration were assessed and the data indicated that LINC02381 up-regulation suppressed cell viability and proliferation while increasing the apoptosis in CRC-originated cell lines. Mechanistically, LINC02381 overexpression was increased PTEN protein levels but decreased phospho-Akt levels. Finally, we proposed a hypothesized model for PI3K signaling regulation by LINC02381. Altogether, the result of this study suggests that LINC02381 might have suppressive effects on human colorectal cancer tumorigenesis partly by regulating PI3K signaling pathway.
       
  • Cartilage acidic protein 1 promotes increased cell viability, cell
           proliferation and energy metabolism in primary human dermal fibroblasts
    • Abstract: Publication date: Available online 18 February 2020Source: BiochimieAuthor(s): Sophia Letsiou, Rute Felix, João C. Cardoso, Liliana Anjos, Ana L. Mestre, Henirique L. Gomes, Deborah M. Power Cartilage acidic protein 1 (CRTAC1) is an extracellular matrix protein of human chondrogenic tissue that is also present in other vertebrates, none-vertebrate eukaryotes and in some prokaryotes. The function of CRTAC1 remains unknown but the protein’s structure indicates a role in cell-cell or cell-matrix interactions and calcium-binding. The aim of the present study was to evaluate the in vitro effects of hCRTAC1 on normal human dermal fibroblasts (NHDF). A battery of in vitro assays (biochemical and PCR), immunofluorescence and a biosensor approach were used to characterize the protein’s biological activities on NHDF cells in a scratch assay. Gene expression analysis revealed that hCRTAC1 protein is associated with altered levels of expression for genes involved in the processes of cell proliferation (CXCL12 and NOS2), cell migration (AQP3 and TNC), and extracellular matrix-ECM regeneration and remodeling (FMOD, TIMP1, FN1) indicating a role for hCRTAC1 in promoting these activities in a scratch assay. In parallel, the candidate processes identified by differential gene transcription were substantiated and extended using Electric cell-substrate impedance sensing (ECIS) technology, immunofluorescence and cell viability assays. Our findings indicate that hCRTAC1 stimulated cell proliferation, migration and ECM production in primary human fibroblasts in vitro.
       
  • An aptamer-based, fluorescent and radionuclide dual-modality probe
    • Abstract: Publication date: Available online 17 February 2020Source: BiochimieAuthor(s): Gui-Xiong Zhang, Yan-Lan Liu, Min Yang, Wen-Shan Huang, Jie-Hua Xu Aptamers which are promising and effective molecular probes, can deliver either fluorescent materials or radionuclides to tumors. This study aimed to develop a novel both fluorescent and radionuclide dual-modality probe based on a truncated aptamer and evaluate its stability and binding affinities in vitro. The aptamer JHIT2 with binding specifically to HepG2 cells was previously generated by Cell-SELEX. Using mfold and RNAstructure software to predict the secondary structure folded by a middle random sequence to truncate the primer sequences at both ends of the aptamer JHIT2 to yield the aptamer JHIT2e, with a similar secondary structure to JHIT2 and the same specificity and affinity as JHIT2. Attaching carboxyfluorescein (FAM) readily to the aptamer JHIT2e and then attaching iodine-131 to the FAM moiety which has multiple sites for iodine labeling to develop a novel both fluorescent and radionuclide dual-modality probe, termed 131I-FAM-JHIT2e. Cell uptake and fluorescence imaging assays in vitro confirmed that 131I-FAM-JHIT2e had both FAM fluorescence signal and radio-activity signal and maintained specific binding ability to the human hepatoma cell line HepG2. This work formed a basis for aptamer-based, dual-modality imaging probe that contains both fluorescent and radionuclide tags, which also is potential for theranostics.Graphical abstractImage 1
       
  • Corrigendum to “A new xanthatin analogue
           1β-hydroxyl-5α-chloro-8-epi-xanthatin induces apoptosis through
           ROS-mediated ERK/p38 MAPK activation and JAK2/STAT3 inhibition in human
           hepatocellular carcinoma” [Biochimie 152C (2018) 43–52]
    • Abstract: Publication date: April–May 2020Source: Biochimie, Volumes 171–172Author(s): Xin-Yi Fang, Hai Zhang, Lin Zhao, Shuai Tan, Qing-Cuo Ren, Lun Wang, Xiao-Fei Shen
       
  • Probing the DNA-binding center of the MutL protein from the Escherichia
           coli mismatch repair system via crosslinking and Förster resonance energy
           transfer
    • Abstract: Publication date: Available online 14 February 2020Source: BiochimieAuthor(s): Maya Monakhova, Alexandra Ryazanova, Vladislav Kunetky, Pingping Li, Evgeniy Shilkin, Olga Kisil, Desirazu N. Rao, Tatiana Oretskaya, Peter Friedhoff, Elena Kubareva As no crystal structure of full-size MutL bound to DNA has been obtained up to date, in the present work we used crosslinking and Förster resonance energy transfer (FRET) assays for probing the putative DNA-binding center of MutL from Escherichia coli. Several single-cysteine MutL variants (scMutL) were used for site-specific crosslinking or fluorophore modification. The crosslinking efficiency between scMutL proteins and mismatched DNA modified with thiol-reactive probes correlated with the distances from the Cys residues to the DNA calculated from a model of MutS–MutL–DNA complex. FRET-based investigation of DNA-binding with different scMutL variants clearly showed the highest signals were detected for the variants MutL(T218C) and MutL(A251C) indicating closeness of the positions 218 and 251 to DNA in the MutL-DNA complex. Indeed, the Cys218 and Cys251 of scMutL were crosslinked to the reactive DNA with the highest yield demonstrating their proximity to DNA in the MutL–DNA complex. The presence of MutS increased the yield of conjugate formation between the MutL variants and the modified DNA due to tighter MutL–DNA interactions caused by MutS binding to MutL.
       
  • The complex interplay between DNA methylation and miRNAs in gene
           expression regulation
    • Abstract: Publication date: Available online 13 February 2020Source: BiochimieAuthor(s): Andrea Fuso, Tiziana Raia, Michela Orticello, Marco Lucarelli The short, non-coding RNAs, also called microRNAs (miRNAs) can bind complementary sequences on cellular mRNAs. The consequence of this binding is generally the degradation of mRNA and the inhibition of its translation. For this reason, miRNAs are included among the epigenetic factors acting as a modulator of gene expression. How miRNAs expression is, in turn, regulated is still the object of active investigation, but DNA methylation, another epigenetic modification, seems to play a central role in this sense. The “one-carbon” metabolism is responsible for the metabolic regulation of trans-methylation reactions and, therefore, DNA methylation. For this reason, to investigate the possible correlations between alterations of the one-carbon metabolism and differential DNA methylation sounds interesting. Moreover, recent evidence indicates that, vice-versa, miRNAs are associated with DNA methylation modulation, in a mutual cross-talk. The present review will discuss the interplay between miRNAs and DNA methylation and its fall-out on gene expression regulation.
       
  • One carbon metabolism and folate transporter genes: Do they factor
           prominently in the genetic etiology of neural tube defects'
    • Abstract: Publication date: Available online 13 February 2020Source: BiochimieAuthor(s): John W. Steele, Sung-Eun Kim, Richard H. Finnell Neural tube defects (NTDs) are a broad class of congenital birth defects that result from the failure of neural tube closure during neurulation. Folic acid supplementation has been shown to prevent the occurrence of NTDs by as much as 70% in some human populations, and folate deficiency in a pregnant woman is associated with increased risk for having an NTD affected infant. Thus, folate transport-related genes and genes involved in the subsequent folate-mediated one carbon metabolic pathway have long been considered primary candidates to study the genetic etiology of human NTDs. Herein, we review the genes involved in folate transport and one carbon metabolism thus far identified as contributing variants that influence human NTD risk, and place these findings in the context of our evolving understanding of the complex genetic architecture underlying these defects.
       
  • Cyclical Amyloid beta-Astrocyte Activity Induces Oxidative Stress in
           Alzheimer’s Disease
    • Abstract: Publication date: Available online 13 February 2020Source: BiochimieAuthor(s): Shalini Elangovan, R.M.Damian Holsinger Glial cell involvement in Alzheimer’s disease (AD) is multi-faceted. The role of astrocytes in AD pathology, both as a causative agent of amyloid-beta (Aβ) production as well as a casualty of dysfunction resulting from the presence of Aβ has been well-delineated. In this review, we explore the influence of oxidative stress in astrocytes and the subsequent effect on Aβ levels in the brain from a perspective of intracellular calcium homeostasis and NADPH oxidase activity. The response of astrocytes to the presence of Aβ as well astrocytic and microglial interaction and inflammatory cytokine release is also discussed, highlighting a cyclical behaviour of these cells in contributing to AD pathogenesis.
       
  • Hypoxia increases the rate of renal gluconeogenesis via hypoxia-inducible
           factor-1-dependent activation of phosphoenolpyruvate carboxykinase
           expression
    • Abstract: Publication date: Available online 8 February 2020Source: BiochimieAuthor(s): Aleksandra Owczarek, Katarzyna Gieczewska, Robert Jarzyna, Adam K. Jagielski, Anna Kiersztan, Andrzej Gruza, Katarzyna Winiarska Although up to 25% of glucose released into circulation in the postabsorptive state comes from renal gluconeogenesis, the regulatory mechanisms of this process are still poorly recognized, comparing to hepatic ones. The aim of the present study was to examine if hypoxia-inducible factor-1 (HIF-1) might be involved in the regulation of glucose de novo synthesis in kidneys. It was found that HK-2 cells (immortalized human kidney proximal tubules, capable of gluconeogenesis/glycogen synthesis) cultured with gluconeogenic substrates either in hypoxia (1% O2) or in the presence of DMOG (an inhibitor of HIF-1α degradation) exhibited increased glycogen content. This phenomenon was not correlated with augmented glucose intake and the effects were reversed by echinomycin (an inhibitor of HIF-1 binding to HRE sequence). As concluded from the measurement of the intracellular content of gluconeogenic intermediates followed by Western blot analysis, under conditions of hypoxia/increased HIF-1 level the activity of phosphoenolpyruvate carboxykinase (PEPCK) was elevated, as a result of increased expression of the cytosolic isoform of PEPCK (PEPCK-C). Chromatin immunoprecipitation (ChIP) analysis proved HIF-1 ability to bind to the promoter region of PEPCK-C gene. The final conclusion that hypoxia/HIF-1 accelerates the rate of renal glucogenesis via the mechanism engaging activation of PEPCK-C expression might be useful in terms of e.g. diabetes treatment, as it is commonly accepted that under diabetic conditions kidneys and liver seem to be equally important sources of glucose synthesized de novo.
       
  • Modification of cardiac transcription factor Gata6 by SUMO
    • Abstract: Publication date: Available online 1 February 2020Source: BiochimieAuthor(s): Huiqiao Chen, Weiyue Sun, Jun Zhu, Hao Yuan, Maoping Chu, Bin Wen SUMOylation, covalent conjugation of small ubiquitin-related modifier (SUMO), has been emerging as a critical posttranslational modification of developmental transcription factors, as well as key regulators in the adult heart. Identifying the SUMOylated targets within cardiac transcription factors will facilitate to unravel the roles of SUMOylation in heart development and disease. Here, we show that Gata6, an essential cardiac transcription factor, can be modified by SUMO in vivo. Mutation of potential SUMOylation sites reveals that a lysine residue at amino acid position 12 of Gata6 severs as the major attachment site for SUMO. Pias1, as an E3 SUMO ligase, preferentially enhances the conjugation of SUMO1 to Gata6 through its RING finger domain. Functional analyses with SUMOylation-deficient mutant indicate that SUMOylation does not affect the subcellular localization but instead represses Gata6 transcriptional activity. Our data suggest that posttranslational modification of Gata6 by SUMO conjugation provides a novel mechanism to regulate Gata6 activity.
       
  • Critical parameters in surface plasmon resonance biosensor development:
           the interaction between estrogen receptor and estrogen response element as
           model
    • Abstract: Publication date: Available online 1 February 2020Source: BiochimieAuthor(s): Sandrine Bayle, David Benimelis, Joel Chopineau, Benoit Roig, Denis Habauzit Estrogenic compounds are contaminants that may be active at low concentrations and are a major concern for environmental quality. They interact with organisms via Estrogen Receptors (ER). Some detection methods which have been developed use the ability of ER to interact with short consensus DNA sequences known as Estrogen Response Elements (ERE). Surface Plasmon Resonance (SPR) based techniques allow detection of interaction without labelled molecule use. Such optical transductors are widely used to convert the biological recognition signals into electric quantifiable signals. In this study, SPR is used to assess signal variation in the presence of estrogenic compounds. The combination of physical properties and biological recognition events (e.g. ER/ERE) permits the development of biosensors. These require several steps: activation of the surface, DNA sequence binding, ERE sequence evaluation, ER preparation, characterization of binding properties and regeneration of the surface. This article focuses on the mode of surface activation, protein-DNA binding conditions and the regeneration of ERE. After giving a summary of the literature concerning the usual conditions employed in these steps, an evaluation of some key parameters is given.
       
  • Brain targeting with docosahexaenoic acid as a prospective therapy for
           neurodegenerative diseases and its passage across blood brain barrier
    • Abstract: Publication date: Available online 31 January 2020Source: BiochimieAuthor(s): Mayssa Hachem, Mounir Belkouch, Amanda Lo Van, Madeleine Picq, Nathalie Bernoud-Hubac, Michel Lagarde Docosahexaenoic acid (DHA, 22:6n-3) is the main omega-3 polyunsaturated fatty acid in brain tissues necessary for common brain growth and function. DHA can be provided to the body through two origins: an exogenous origin, from direct dietary intakes and an endogenous one, from the bioconversion of the essential α-linolenic acid (ALA, 18:3n-3) in the liver. In humans, the biosynthesis of DHA from its precursor ALA is very low. A reduction in the cerebral amount of DHA is detected in patients suffering from neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Considering the vital functions of DHA for the brain, new methodologies to target the brain with DHA offers encouraging perceptions in the improvement of precautionary and therapeutic approaches for neurodegenerative diseases. The aim of the present review was to provide better understanding of the cerebral uptake of DHA in different form including free fatty acids, Lysophosphatidylcholines LysoPC-DHA as well as structured phospholipids. First, we explored the special structure of the blood-brain barrier BBB, BBB being a physical and metabolic barrier with restrictive properties. Then, we discussed the incorporation of DHA into the membrane phospholipids of the brain, the neuroprotective and therapeutic effect of DHA for neurological diseases.
       
  • On the Simultaneous Activation of Agrobacterium tumefaciensADP-glucose
           Pyrophosphorylase by Pyruvate and Fructose 6-phosphate
    • Abstract: Publication date: Available online 31 January 2020Source: BiochimieAuthor(s): Matías D. Asencion Diez, Carlos M. Figueroa, María C. Esper, Romila Mascarenhas, Mabel C. Aleanzi, Dali Liu, Miguel A. Ballicora, Alberto A. IglesiasABSTRACTBacterial ADP-glucose pyrophosphorylases are allosterically regulated by metabolites that are key intermediates of central pathways in the respective microorganism. Pyruvate (Pyr) and fructose 6-phosphate (Fru6P) activate the enzyme from Agrobacterium tumefaciens by increasing Vmax about 10- and 20-fold, respectively. Here, we studied the combined effect of both metabolites on the enzyme activation. Our results support a model in which there is a synergistic binding of these two activators to two distinct sites and that each activator leads the enzyme to distinct active forms with different properties. In presence of both activators, Pyr had a catalytically dominant effect over Fru6P determining the active conformational state. By mutagenesis we obtained enzyme variants still sensitive to Pyr activation, but in which the allosteric signal by Fru6P was disrupted. This indicated that the activation mechanism for each effector was not the same. The ability for this enzyme to have more than one allosteric activator site, active forms, and allosteric signaling mechanisms is critical to expand the evolvability of its regulation. These synergistic interactions between allosteric activators may represent a feature in other allosteric enzymes.
       
  • Calreticulin protects insulin against reductive stress in vitro and in
           MIN6 cells
    • Abstract: Publication date: Available online 29 January 2020Source: BiochimieAuthor(s): Midori Ikezaki, Shiho Minakata, Kazuchika Nishitsuji, Shotaro Tabata, In-Sook Lee Matsui, Maki Takatani, Jiro Usukura, Yukishige Ito, Yoshito Ihara Oxidative folding of proinsulin in the endoplasmic reticulum (ER) is critical for the proper sorting and secretion of insulin from pancreatic β-cells. Here, by using non-cell-based insulin aggregation assays and mouse insulinoma-derived MIN6 cells, we searched for a candidate molecular chaperone for (pro)insulin when its oxidative folding is compromised. We found that interaction between insulin and calreticulin (CRT), a lectin that acts as an ER-resident chaperone, was enhanced by reductive stress in MIN6 cells. Co-incubation of insulin with recombinant CRT prevented reductant-induced aggregation of insulin. Furthermore, lysosomal degradation of proinsulin, which was facilitated by dithiothreitol-induced reductive stress, depended on CRT in MIN6 cells. Together, our results suggest that CRT may be a protective molecule against (pro)insulin aggregation when oxidative folding is defective, e.g. under reductive stress conditions, in vitro and in cultured cells. Because CRT acts as a molecular chaperone for not only glycosylated proteins but also non-glycosylated polypeptides, we also propose that (pro)insulin is a novel candidate client of the chaperone function of CRT.
       
  • Neutralization of a bothropic PLA2-like protein by caftaric acid, a novel
           potent inhibitor of ophidian myotoxicity
    • Abstract: Publication date: Available online 22 January 2020Source: BiochimieAuthor(s): Fábio F. Cardoso, Antoniel A.S. Gomes, Thiago R. Dreyer, Walter L.G. Cavalcante, Maeli Dal Pai, Márcia Gallacci, Marcos R.M. Fontes Envenoming by snakebite is an important global health issue that has received little attention, leading the World Health Organization to naming it as neglected tropical disease. Several snakebites present serious local symptoms manifested on victims that may not be efficiently neutralized by serum therapy. Phospholipase A2-like (PLA2-like) toxins are present in Viperidae venoms and are responsible for local myotoxic activity. Herein, we investigated the association between BthTX-I toxin and caftaric acid (CFT), a molecule present in plants. CFT neutralized neuromuscular blocking and muscle-damaging activities promoted by BthTX-I. Calorimetric and light-scattering assays demonstrated that CFT inhibitor interacted with dimeric BthTX-I. Bioinformatics simulations indicated that CFT inhibitor binds to the toxin’s hydrophobic channel (HCh). According to the current myotoxic mechanism, three different regions of PLA2-like toxins have specific tasks: protein allosteric activation (HCh), membrane dockage (MDoS), and membrane rupture (MDiS). We propose CFT inhibitor interferes with the allosteric activation, which is related to the conformation change leading to the exposure/alignment of MDoS/MDiS region. This is the first report of a PLA2-like toxin fully inhibited by a compound that interacts only with its HCh region. Thus, CFT is a novel candidate to complement serum therapy and improve the treatment of snakebite.
       
  • Biophysical approaches for exploring lipopeptide-lipid interactions
    • Abstract: Publication date: Available online 21 January 2020Source: BiochimieAuthor(s): Sathishkumar Munusamy, Renaud Conde, Brandt Bertrand, Carlos Munoz-Garay In recent years, lipopeptides (LPs) have attracted a lot of attention in the pharmaceutical industry due to their broad-spectrum of antimicrobial activity against a variety of pathogens and their unique mode of action. This class of compounds has enormous potential for application as an alternative to conventional antibiotics and for pest control. Understanding how LPs work from a structural and biophysical standpoint through investigating their interaction with cell membranes is crucial for the rational design of these biomolecules. Various analytical techniques have been developed for studying intramolecular interactions with high resolution. However, these tools have been barely exploited in lipopeptide-lipid interactions studies. These biophysical approaches would give precise insight on these interactions. Here, we reviewed these state-of-the-art analytical techniques. Knowledge at this level is indispensable for understanding LPs activity and particularly their potential specificity, which is relevant information for safe application. Additionally, the principle of each analytical technique is presented and the information acquired is discussed. The key challenges, such as the selection of the membrane model are also been briefly reviewed.Graphical abstractImage 1
       
  • Moderately elevated first trimester fasting plasma total homocysteine is
           associated with increased probability of miscarriage. The Reus-Tarragona
           Birth Cohort Study
    • Abstract: Publication date: Available online 18 January 2020Source: BiochimieAuthor(s): Pere Cavallé-Busquets, Montserrat Inglés-Puig, Joan Fernandez-Ballart, Júlia Haro-Barceló, Alejandra Rojas-Gómez, Carla Ramos-Rodriguez, Monica Ballesteros, Klaus Meyer, Per M. Ueland, Michelle M. Murphy The association between elevated early pregnancy fasting plasma total homocysteine (tHcy) and miscarriage risk was investigated prospectively in participants (n=544) from the Reus-Tarragona Birth Cohort study. Pregnancy was confirmed before 12 gestational weeks (GW) by ultrasound scan and a fasting blood sample collected. Pregnancies with complications other than miscarriages were excluded. Miscarriages were diagnosed by ultrasound scan and gestational age at the time of miscarriage estimated by embryo size, where possible. Cases in which blood samples were collected more than a week after the miscarriage, or the miscarriage was of known cause, were excluded.Fasting plasma folate, vitamin B12, tHcy, cotinine (biomarker of smoking), red blood cell (RBC) folate, MTHFR 677C>T (rs1801133) and SLC19A1 80G>A (rs1051266) genotypes were determined.The exposed group consisted of participants with first trimester tHcy ≥P90 (7.1 μmol/L) (n=57) and unexposed of those with tHcy
       
  • Metabolic memory and diabetic nephropathy: beneficial effects of natural
           epigenetic modifiers
    • Abstract: Publication date: Available online 16 January 2020Source: BiochimieAuthor(s): Kriti Kushwaha, Sandeep Sharma, Jeena Gupta Nephropathy is one of the most frequent complications of chronic diabetes. The main reason for nephropathy despite being hyperglycemia, but it progresses even after good glycemic control has been achieved in diabetic patients. The effects of prior exposure to high blood glucose conditions depend upon the severity and duration of this exposure, indicating a “metabolic memory’ phenomenon. Hyperglycemia not only increases oxidative stress but is also alleged to start several biochemical anomalies and alter gene expression associated with metabolic homeostasis. High glucose levels induce epigenetic modifications that alter gene expression without changing DNA sequences. These epigenetic modifications have shown to be reversible and have the potential to cease adverse effects if good glycemic control is achieved from initiation of diabetes. However, if good glycemic control is not achieved for months, these modifications stand firm to reversals. Therapies and drugs have been in use to prevent epigenetic modifications and oxidative stress, which also helped in ameliorating diabetic nephropathy. But these synthetic drugs are loaded with side effects like increased body weight, kidney dysfunction etc. So phytochemicals are emerging as alternatives and many of them have already been used to treat nephropathy. But still, there is rigorous need to evaluate phytochemicals which can regulate epigenetic events and have the potential to decelerate the further progression of these life-threatening diseases. In this review article we discuss the potential epigenetic modifiers from plants that can erase metabolic memory and can thus be protective against diabetic nephropathy.Graphical abstractSchematic diagram shows the role of hyperglycemia-induced epigenetic changes in causing metabolic memory and diabetic nephropathy further highlighting the protective effects of phytochemicals.Image 1
       
  • Degenerate consensus sequences in the 3′-untranslated regions of
           cellular mRNAs as specific motifs potentially involved in the
           YB-1-mediated packaging of these mRNAs
    • Abstract: Publication date: Available online 13 January 2020Source: BiochimieAuthor(s): Alexander V. Gopanenko, Alexey A. Malygin, Olga A. Kossinova, Alexey E. Tupikin, Marsel R. Kabilov, Galina G. KarpovaAbstractThe multifunctional protein YB-1 has previously been shown to be the only protein of the cytoplasmic extract of HEK293 cells, which is able to specifically interact with imperfect RNA hairpins containing motifs that are often found in exosomal (e) RNAs. In addition, it has been revealed that similar hairpins formed by degenerate consensus sequences corresponding to three eRNA-specific motifs are responsible for the cooperative binding of YB-1 to RNA in vitro. Here, using the photoactivatable-ribonucleoside enhancing cross-linking and immunoprecipitation method applied to HEK293 cells producing FLAG-labeled YB-1, we identified mRNAs cross-linked to YB-1 in vivo and then carried out a search for the aforementioned sequences in the regions of the YB-1 cross-linking sites. It turned out that many of the mRNAs found cross-linked to YB-1 encode proteins associated with various regulatory processes, including responses to stress. More than half of all cross-linked mRNAs contained degenerate consensus sequences, which were preferably located in 3′-untranslated regions (UTRs), where most of the YB-1 cross-linking sites appeared, although not close to these sequences. Furthermore, YB-1 was mainly cross-linked to those mRNAs with degenerate consensus sequences, which could be classified as packaged because their translation levels were low compared to cellular levels. This suggests that the cooperative binding of YB-1 to mRNAs through the above sequences probably triggers the well-known multimerization of YB-l, leading to the packaging of these mRNAs. Thus, our findings indicate a previously unknown link between the degenerate consensus sequences present in the 3′-UTRs of many cytoplasmic mRNAs and YB-1-mediated translational silencing.
       
  • Naturally occurring cinnamic acid derivatives prevent amyloid
           transformation of alpha-synuclein
    • Abstract: Publication date: Available online 13 January 2020Source: BiochimieAuthor(s): Maria Medvedeva, Kseniya Barinova, Aleksandra Melnikova, Pavel Semenyuk, Vasillii Kolmogorov, Petr Gorelkin, Alexander Erofeev, Vladimir MuronetzAbstractIn search of the compounds that interfere with amyloid transformation of alpha-synuclein, 9 natural and synthetic cinnamic acid derivatives were studied. They are structurally similar to a half of curcumin, which has pronounced anti-aggregatory and anti-amyloid effects. We have shown that some of these derivatives prevent ovine prion protein amyloidization. Subsequently, thioflavin T binding assay showed that 3 out of 9 studied compounds effectively prevented amyloid transformation of alpha-synuclein with IC50 of 13, 50 and 251 μM. Molecular modeling approach revealed possible binding sites of the three selected ligands with alpha-synuclein fibrils, while monomeric alpha-synuclein does not bind to the ligands according to experimental results. This led us to believe that compounds may act by changing the structure of primary aggregates, preventing the formation of full-length fibrils. The inhibiting effect of the ligands on aggregation of alpha-synuclein was further confirmed by monitoring aggregation via turbidimetry, susceptibility to proteolytic cleavage, changes in beta-sheet content, and scanning ion-conductance microscopy. Studied derivatives were not cytotoxic, and, moreover, two studied compounds (ferulic and 3,4-dimethoxycinnamic acid) are found in plant sources and are natural metabolites present in human blood, so they can be promising candidate drugs for synucleinopathies, including Parkinson's disease.
       
  • Detection and in vitro studies of Cucurbita maxima phloem serpin-1
           RNA-binding properties
    • Abstract: Publication date: Available online 11 January 2020Source: BiochimieAuthor(s): Eugeny A. Tolstyko, Alexander A. Lezzhov, Anna V. Pankratenko, Marina V. Serebryakova, Andrey G. Solovyev, Sergey Y. MorozovAbstractApart from being a conduit for photoassimilate transport in plants, the phloem serves as a pathway for transport of proteins and RNAs from sites of their synthesis to distant plant parts. As demonstrated for mRNAs and small RNAs such as miRNA and siRNA, their phloem transport is largely involved in responses to environmental cues including stresses and pathogen attacks. RNA molecules are believed to be transported in the phloem in the form of complexes with RNA-binding proteins; however, proteins forming such complexes are generally poorly studied. Here, we demonstrate that the Cucurbita maxima phloem serpin-1 (CmPS1), which has been previously described as a functional protease inhibitor capable of long-distance transport via the phloem, is able to bind RNA in vitro. Among different RNAs tested, CmPS1 exhibits a preference for imperfect RNA duplexes and the highest affinity to tRNA. A characteristic complex formed by CmPS1 with tRNA is not observed upon CmPS1 binding to tRNA-like structures of plant viruses. Mutational analysis demonstrates that the CmPS1 N-terminal region is not involved in RNA binding. Since antithrombin-III, the human protease inhibitor of serpin family most closely sequence-related to CmPS1, is found to be unable to bind RNA, one can suggest that, in its evolution, CmPS1 has gained the RNA binding capability as an additional function likely relevant to its specific activities in the plant phloem.
       
  • Deciphering the essentiality and function of SxSx motif in
           Mycobacterium tuberculosis UvrB
    • Abstract: Publication date: Available online 8 January 2020Source: BiochimieAuthor(s): Manoj Thakur, K. MuniyappaABSTRACTThe UvrB subunit is a central component of the UvrABC incision complex and plays a pivotal role in damage recognition, strand excision and repair synthesis. A conserved structural motif (the SxSx motif) present in UvrB is analogous to a similar motif (TxGx) in the helicases of superfamily 2, whose function is not fully understood. To elucidate the significance of the SxSx (Ser143-Val144-Ser145-Cys146) motif in Mycobacterium tuberculosis UvrB (MtUvrB), different variants of MtUvrB subunit were constructed and characterized. The SxSx motif indeed was found to be essential for MtUvrB function: while Ser143 and Cys146 residues within this motif were crucial for MtUvrB function, Ser145 plays an important but less essential role. The SxSx motif-deleted mutant was drastically attenuated and three single (S143A, S145A and C146A) mutants and a double (S143A/S145A) mutant exhibited various degrees of severity in their DNA-binding, DNA helicase and ATPase activities. Taken together, these results highlight a hitherto unrecognized role for SxSx motif in the catalytic activities of UvrB.Graphical abstractImage 1
       
  • Hepatic glycerol metabolism is early reprogrammed in rat liver cancer
           development
    • Abstract: Publication date: Available online 7 January 2020Source: BiochimieAuthor(s): Florencia Lorenzetti, Alejo M. Capiglioni, Raúl A. Marinelli, María Cristina Carrillo, María de Luján AlvarezAbstractEvidence shows that oral glycerol supplementation during the early stages of rat liver cancer reduces the growth of preneoplastic lesions. Besides, human hepatocellular carcinoma (HCC) cells display decreased expression of glycerol channel aquaporin 9 (AQP9) and also diminished glycerol-3-phosphate (G3P) content. According to this, we analyzed glycerol metabolism during the initial stages of rat liver carcinogenesis. Wistar rats were subjected to a 2-phase model of hepatocarcinogenesis (initiated-promoted, IP group) or left untreated (control, C group). Different features of glycerol metabolism were compared between both groups. IP animals showed increased plasma free glycerol levels and liver AQP9 protein expression. Also, IP rats showed increased glycerol kinase (GK) and glycerol-3-phosphate dehydrogenase (GPDH) hepatic activities. Gluconeogenesis from glycerol both in vivo and in isolated perfused liver was higher in rats having liver preneoplasia. Nevertheless, preneoplastic foci notably reduced AQP9 and GK protein expressions, displaying a reduced ability to import glycerol and to convert it into G3P, as a way to preserve preneoplastic hepatocytes from the deleterious effect of G3P. In conclusion, the metabolic shift that takes place in the initial stages of liver cancer development comprises an increased hepatic utilization of glycerol for gluconeogenesis. Enhanced glucose production from glycerol is mostly carried out by the surrounding non-preneoplastic tissue and can be used as an energy source for the early transformed liver cells.
       
  • Revisiting prochirality
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Raymond S. Ochs, Tanaji T. TaleleAbstractWe propose a new model for prochirality that satisfies all known examples: the prochiral plane. This plane contains the prochiral carbon and defines two separate faces for chemical modification. We extend this to enzyme catalysis, replacing the “three point attachment” hypothesis and its variants. Once a prochiral substrate is fixed on an enzyme surface, the asymmetry of the enzyme provides reactants exclusively on one side of the prochiral plane, producing an enantiomerically pure chiral product. The aconitase reaction is detailed as an example, using molecular modeling and its known enzymatic mechanism. We show that the prochiral substrate for this enzyme is not citrate, but rather cis-aconitate. The number of interaction points of cis-aconitate is not relevant to prochirality, but rather to substrate specificity. A second detailed example is the enzyme fumarase; here the substrate fumarate has only two binding sites, but is nonetheless fixed onto the enzyme and has a defined prochiral plane. We also provide a literature survey of more prochiral substrates, all of which have sp2 hybridized carbon and contain a prochiral plane. An example of a prochiral unnatural substrate for sphingosine kinase 2, fingolimod, has an sp3 hybridized prochiral carbon and also contains a prochiral plane. Finally, we provide an intuitive example of a prochiral physical object, a coffee cup, interacting with one hand and lip.
       
  • Antitermination protein P7 of bacteriophage Xp10 distinguishes different
           types of transcriptional pausing by bacterial RNA polymerase
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Maria Prostova, Andrey Kulbachinskiy, Daria EsyuninaAbstractBacteriophage-encoded transcription antiterminators play essential roles in the regulation of gene expression during infection. Here, we characterize the effects of the antiterminator protein P7 of bacteriophage Xp10 on transcriptional pausing by Xanthomonas oryzae RNA polymerase (RNAP) at different types of pause-inducing signals. When acting alone, P7 inhibits only hairpin-stabilized pauses, likely by preventing hairpin formation. In the presence of NusA, P7 also suppresses backtracking-stabilized pauses and the his elemental pause, but not the consensus elemental pause, suggesting that these pause signals may be mechanistically different. Thus, P7 and other bacteriophage proteins that bind near the RNA exit channel of RNAP have evolved to regulate transcription by suppressing RNAP pausing at a subset of regulatory signals, and to co-opt NusA in doing so.
       
  • Deletion of CDR1 reveals redox regulation of pleiotropic drug resistance
           in Candida glabrata
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Kseniia V. Galkina, Michiyo Okamoto, Hiroji Chibana, Dmitry A. Knorre, Susumu KajiwaraMicrobial cells sense the presence of xenobiotics and, in response, upregulate genes involved in pleiotropic drug resistance (PDR). In yeast, PDR activation to a major extent relies on the transcription factor Pdr1. In addition, many xenobiotics induce oxidative stress, which may upregulate PDR independently of Pdr1 activity. Mitochondria are important sources of reactive oxygen species under stressful conditions. To evaluate the relevance of this redox pathway, we studied the activation of PDR in the yeast Candida glabrata, which we treated with a mitochondrially targeted antioxidant plastoquinonyl-decyl-triphenylphosphonium and dodecyltriphenylphosphonium (C12TPP) as a control. We found that both compounds induced activation of PDR genes and decreased the intracellular concentration of the PDR transporter substrate Nile red. Interestingly, the deletion of PDR transporter gene CDR1 inhibited the decrease in Nile red accumulation induced by antioxidant plastoquinonyl-decyl-triphenylphosphonium but not that by C12TPP. Moreover, antioxidant alpha-tocopherol inhibited C12TPP-mediated activation of PDR in Δcdr1 but not in the wild-type strain. Furthermore, pre-incubation of yeast cells with low concentrations of hydrogen peroxide induced a decrease in the intracellular concentration of Nile red in Δcdr1 and Δpdr1 as well as in control cells. Deletion of PDR1 inhibited the C12TPP-induced activation of CDR1 but not that of FLR1, which is a redox-regulated PDR transporter gene. It appears that disruption of the PDR1/CDR1 regulatory circuit makes auxiliary PDR regulation mechanisms crucial. Our data suggest that redox regulation of PDR is dispensable in wild-type cells because of redundancy in the activation pathways, but is manifested upon deletion of CDR1.Graphical abstractImage 1
       
  • Cerebrospinal fluid: Profiling and fragmentation of gangliosides by ion
           mobility mass spectrometry
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Mirela Sarbu, Shannon Raab, Lucas Henderson, Dragana Fabris, Željka Vukelić, David E. Clemmer, Alina D. ZamfirAbstractThe proximity of cerebrospinal fluid (CSF) with the brain, its permanent renewal and better availability for research than tissue biopsies, as well as ganglioside (GG) shedding from brain to CSF, impelled lately the development of protocols for the characterization of these glycoconjugates and discovery of central nervous system biomarkers expressed in CSF. Currently, the investigation of CSF gangliosides is focused on concentration measurements of the predominant classes and much less on their profiling and structural analysis.Since we have demonstrated recently the high performance of ion mobility separation mass spectrometry (IMS MS) for compositional and structural determination of human brain GGs, in the present study we have implemented for the first time IMS MS for the exploration of human CSF gangliosidome, in order to generate the first robust mass spectral database of CSF gangliosides. IMS MS separation and screening revealed 113 distinct GG species in CSF, having similar compositions to the species detected in human brain. In comparison with the brain tissue, we have discovered in CSF several components containing fatty acids with odd number of carbon atoms and/or short glycan chains. By tandem MS (MS/MS) we have further analyzed the structure of GD3(d18:1/18:0) and GD2(d18:1/18:0), two glycoforms exhibiting short carbohydrate chains found in CSF, but discovered and characterized previously in brain as well. According to the present results, human CSF and brain show a similar ganglioside pattern, a finding that might be useful in clinical research focused on discovery of ganglioside species associated to neurodegenerative diseases and brain tumors.
       
  • The flanking peptides issue from the maturation of the human islet amyloid
           polypeptide (hIAPP) slightly modulate hIAPP-fibril formation but not
           hIAPP-induced cell death
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Shadai Salazar Vazquez, Bertrand Blondeau, Pierre Cattan, Mathieu Armanet, Ghislaine Guillemain, Lucie KhemtemourianAbstractType 2 diabetes mellitus is a disease characterized by the formation of amyloid fibrillar deposits consisting mainly in human islet amyloid polypeptide (hIAPP), a peptide co-produced and co-secreted with insulin. hIAPP and insulin are synthesized by pancreatic β cells initially as prehormones resulting after sequential cleavages in the mature peptides as well as the two flanking peptides (N- and C-terminal) and the C-peptide, respectively. It has been suggested that in the secretory granules, the kinetics of hIAPP fibril formation could be modulated by some internal factors. Indeed, insulin is known to be a potent inhibitor of hIAPP fibril formation and hIAPP-induced cell toxicity. Here we investigate whether the flanking peptides could regulate hIAPP fibril formation and toxicity by combining biophysical and biological approaches. Our data reveal that both flanking peptides are not amyloidogenic. In solution and in the presence of phospholipid membranes, they are not able to totally inhibit hIAPP-fibril formation neither hIAPP-membrane damage. In the presence of INS-1 cells, a rat pancreatic β-cell line, the flanking peptides do not modulate hIAPP fibrillation neither hIAPP-induced cell death while in the presence of human islets, they have a slightly tendency to reduce hIAPP fibril formation but not its toxicity. These data demonstrate that the flanking peptides do not strongly contribute to reduce mature hIAPP amyloidogenesis in solution and in living cells, suggesting that other biochemical factors present in the cells must act on mature hIAPP fibril formation and hIAPP-induced cell death.
       
  • SIRT1/PGC-1 pathway activation triggers autophagy/mitophagy and attenuates
           oxidative damage in intestinal epithelial cells
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Danyang Liang, Yisha Zhuo, Zeheng Guo, Lihua He, Xueyi Wang, Yulong He, Lexing Li, Hanchuan DaiOxidative stress leads to intestinal epithelial cells damage, which induces tight junction injury and systemic endogenous stress syndrome. The evidence suggests that SIRT1/PGC-1α pathway is closely associated with oxidative damage. However, the mechanism in protecting intestinal epithelial cells against oxidative stress dependant on autopahgy/mitophagy remains to be elucidated. In the current study, we investigated the functional role of SIRT1/PGC-1α pathway on regulation of autopahgy/mitophagy and tight junction protein expression underlying the oxidative dysfunction in porcine intestinal epithelial cells (IPEC-1). Results demonstrated that H2O2 exposure caused high accumulation of ROS, with a decrease of mitochondrial membrane potential and an inhibition of the tight junction molecules in IPEC-1 cells. Also, COX IV mRNA expression and SIRT1/PGC-1α pathway were suppressed. Autophagy and PINK1/Parkin dependant-mitophagy were activated following H2O2 treatment. Further research indicated that activation of SIRT1/PGC-1α pathway caused by specific activator SRT 1720 resulted in elevating autophagy/mitophagy related markers and SIRT1 inhibitor EX 527 reversed these effects. Additionally, SIRT1 activation significantly suppressed the ROS generation, leading to increase mitochondrial membrane potential and COX IV expression. Most importantly, the expression of tight junction molecules contributing to maintain intestinal barrier integrity was significantly up-regulated. Collectively, these findings indicated that autophagy/mitophagy elevation caused by SIRT1/PGC-1α pathway activation might be a protective mechanism to increase tight junction integrity against oxidative stress-mediated ROS production in IPEC-1 cells.Graphical abstractImage 1
       
  • Four paralogous Gfh factors in the extremophilic bacterium Deinococcus
           peraridilitoris have distinct effects on various steps of transcription
    • Abstract: Publication date: March 2020Source: Biochimie, Volume 170Author(s): Aleksei Agapov, Andrey KulbachinskiyAbstractGre factors are ubiquitous transcription regulators that stimulate co-transcriptional RNA cleavage by bacterial RNA polymerase (RNAP). Here, we show that the stress-resistant bacterium Deinococcus peraridilitoris encodes four Gre factor homologs, Gfh proteins, that have distinct effects on transcription by RNAP. Two of the factors, Gfh1α and Gfh2β inhibit transcription initiation, and one of them, Gfh1α can also regulate transcription elongation. We show that this factor strongly stimulates transcriptional pausing and intrinsic termination in the presence of manganese ions but has no effect on RNA cleavage. Thus, some Gfh factors encoded by Deinococci serve as lineage-specific transcription inhibitors that may play a role in stress resistance, while the functions of others remain to be discovered.
       
  • Strand displacement DNA synthesis by DNA polymerase gp90 exo― of
           Pseudomonas aeruginosa phage 1
    • Abstract: Publication date: Available online 3 January 2020Source: BiochimieAuthor(s): Chenyang Mi, Shuming Zhang, Wenxin Huang, Mengyuan Dai, Zili Chai, Wang Yang, Shanshan Deng, Lin Ao, Huidong ZhangAbstractStrand displacement DNA synthesis is essential for DNA replication. Gp90, the sole DNA polymerase of Pseudomonas aeruginosa phage 1, can bypass multiply DNA lesions. However, whether it can perform strand displacement synthesis is still unknown. In this work, we found that gp90 exo― could perform strand displacement synthesis, albeit its activity and processivity were lower than those of primer extension. Gp90 exo― itself could not unwind Y-shaped or fork DNA. Tail and gap at DNA fork were necessary for efficient synthesis. High GC content obviously inhibited strand displacement synthesis. Consecutive GC sequence at the entrance of fork showed more inhibition effect on DNA synthesis than that in the downstream DNA fork. The fraction of productive polymerase and DNA complex (A values) was higher for fork than gap; while their average extension rates (kp values) were similar. However, both A and kp values were lower than those for the primer/template (P/T) substrate. The binding of gp90 exo― to fork was tighter than P/T or gap in the absence of dATP. In the presence of dATP to form ternary complex, the binding affinity of gp90 exo― to P/T or gap was increased compared with that in the binary complex. Abasic site, 8-oxoG, and O6-MeG inhibited and even blocked strand displacement synthesis. This work shows that gp90 exo― could perform strand displacement DNA synthesis at DNA fork, discovering the presence of new functions of PaP1 DNA polymerase in DNA replication and propagation of PaP1.
       
  • Multiple catalytic activities of human 17β-hydroxysteroid dehydrogenase
           type 7 respond differently to inhibitors
    • Abstract: Publication date: Available online 27 December 2019Source: BiochimieAuthor(s): Terenzio Ferrante, Salvatore Adinolfi, Giulia D’Arrigo, Donald Poirier, Martina Daga, Marco Lucio Lolli, Gianni Balliano, Francesca Spyrakis, Simonetta Oliaro-BossoCholesterol biosynthesis is a multistep process in mammals that includes the aerobic removal of three methyl groups from the intermediate lanosterol; one from position 14 and two from position 4. During the demethylations at position 4, a 3-ketosteroid reductase catalyses the conversion of both 4-methylzymosterone and zymosterone to 4-methylzymosterol and zymosterol, respectively, restoring the alcoholic function of lanosterol, which is also maintained in cholesterol. Unlike other eukaryotes, mammals also use the same enzyme as an estrone reductase that can transform estrone (E1) into estradiol. This enzyme, named 17β-hydroxysteroid dehydrogenase type 7 (HSD17B7), is therefore a multifunctional protein in mammals, and one that belongs to both the HSD17B family, which is involved in steroid-hormone metabolism, and to the family of post-squalene cholesterol biosynthesis enzymes.In the present study, a series of known inhibitors of human HSD17B7's E1-reductase activity have been assayed for potential inhibition against 3-ketosteroid reductase activity. Surprisingly, the assayed compounds lost their inhibition activity when assayed in HepG2 cells that were incubated with radiolabelled acetate and against the recombinant overexpressed human enzyme incubated with 4-methylzymosterone (both radiolabelled and not). Preliminary kinetic analyses suggest a mixed or non-competitive inhibition on the E1-reductase activity, which is in agreement with Molecular Dynamics simulations. These results raise questions about the mechanism(s) of action of these possible inhibitors, the enzyme dynamic regulation and the interplay between the two activities.Graphical abstractImage 1
       
  • Classical homocystinuria: From cystathionine beta-synthase deficiency to
           novel enzyme therapies
    • Abstract: Publication date: Available online 16 December 2019Source: BiochimieAuthor(s): Erez M. Bublil, Tomas MajtanAbstractGenetic defects in cystathionine beta-synthase (CBS), a key enzyme of organic sulfur metabolism, result in deficiency of CBS activity and a rare inborn error of metabolism called classical homocystinuria (HCU). HCU is characterized by massive accumulation of homocysteine, an intermediate of methionine metabolism, and multisystemic clinical symptoms. Current treatment options for HCU are very limited and often inefficient, partially due to a low patient compliance with very strict dietary regimen. Novel therapeutic approaches are needed to cope with the toxic accumulation of homocysteine and restoration of a healthy metabolic balance. Human CBS is a complex intracellular multimeric enzyme that relies on three cofactors (heme, pyridoxal-5′-phosphate and S-adenosylmethionine) for proper function. Engineering and chemical modification of human CBS yielded OT-58, a first-in-class enzyme therapy candidate for HCU. Pre-clinical testing of OT-58 showed its substantial efficacy in lowering plasma and tissue concentrations of homocysteine, improving metabolic balance and correcting clinical symptoms of HCU. In addition, OT-58 showed great safety and toxicity profile when administered to non-human primates. Overwhelmingly positive and extensive pre-clinical package propelled OT-58 into a first-in-human clinical trial, which started on January 2019. In a meantime, other enzyme therapies based on modified human cystathionine gamma-lyase or erythrocyte-encapsulated bacterial methionine gamma-lyase have shown efficacy in decreasing plasma homocysteine in HCU mice. In addition, gene therapy approaches using adenovirus or minicircle DNA have been evaluated in HCU. In this review, we summarize the current efforts developing novel therapies for HCU to address a high unmet medical need among HCU patients.
       
  • The Role of Heparin/Heparan Sulphate in the IFN-γ-led Arena
    • Abstract: Publication date: Available online 30 November 2019Source: BiochimieAuthor(s): Kening Xu, Lan JinIFN-γ (Interferon-gamma) is a pleiotropic cytokine. It is often involved in a variety of physiological processes by binding to the cell surface transmembrane receptor (IFN-γR) to initiate a series of signalling pathways that transmit external signals from cell surface receptors to the cell nucleus. Heparan sulphate (HS), a highly sulphated linear polysaccharide, is ubiquitous on the mammalian cell surface and extracellular matrix. Electrostatic interactions can be generated between the highly sulphated HS region and specific basic amino acid residues in the IFN-γ structure, thereby detaining IFN-γ on the cell surface, and the concentration of IFN-γ on the cell surface is thus, changed. IFN-γ retained on the cell surface will optimize the binding of IFN-γ to the transmembrane receptor resulting in high efficiency signalling. Heparin is a glycosaminoglycan with a structure similar to HS. The structural similarity provides a basis for modelling exogenous heparin dependence for interference with IFN-γ function. This model can be summarized as follows: First, the competitive binding effect; heparin bound to cytokines by competing with membrane-associated HS, causes a decrease in cytokine concentration on the cell surface. Second, the principle of priority occupancy; heparin can occupy the receptor binding site on cytokines, partially preventing the IFN-γ-IFN-γR interaction. These two models interfere with IFN-γ signal transmission. To decipher the mechanism by which heparin influences IFN-γ activity, studies of the structure-activity relationship are in progress. This paper summarizes research progress on the IFN-γ signalling pathway, heparin interference with IFN-γ activity and the structure-activity relationship between heparin and IFN-γ.Graphical abstractImage 1
       
  • Dietary choline is related to increased risk of acute myocardial
           infarction in patients with stable angina pectoris
    • Abstract: Publication date: Available online 7 November 2019Source: BiochimieAuthor(s): Anthea Van Parys, Vegard Lysne, Gard Frodahl Tveitevåg Svingen, Per Magne Ueland, Indu Dhar, Jannike Øyen, Jutta Dierkes, Ottar K. NygårdHigh plasma choline has been associated with the metabolic syndrome and risk of chronic diseases, including cardiovascular disease. However, dietary choline is not correlated with choline plasma concentrations, and there are few studies and contradictory evidence regarding dietary choline and cardiovascular events. In addition, a recommended dietary allowance for choline has not been established and remains a point of contention.This study assessed the association between dietary choline, including choline forms, and risk of incident acute myocardial infarction (AMI) in patients with suspected stable angina pectoris (SAP).In total 1981 patients (80% men, median age 62) from the Western Norway B Vitamin Intervention Trial were included in this analysis. Information on dietary choline was obtained using a 169-item food frequency questionnaire. The Cardiovascular Disease in Norway project provided data on AMI. Risk associations were estimated using Cox-regression analysis using energy-adjusted choline intake.Median (25th, 75th percentile) total energy-adjusted choline intake was 288 (255, 326) mg/d. During a median (25th, 75th percentile) follow-up of 7.5 (6.3, 8.8) years, 312 (15.7%) patients experienced at least one AMI. Increased intakes of energy-adjusted choline (HR [95% CI] per 50 mg increase 1.11 [1.03, 1.20]), phosphatidylcholine (HR per 50 mg increase 1.24 [1.08, 1.42]) and sphingomyelin (HR per 5 mg increase 1.16 [1.02, 1.31]) were associated with higher AMI risk.Higher dietary intakes of total choline, phosphatidylcholine and sphingomyelin were associated with increased risk of AMI in patients with SAP. Future studies are necessary to explore underlying mechanisms for this observation.Graphical abstractImage 1
       
 
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