Subjects -> BIOLOGY (Total: 3174 journals)
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BIOLOGY (1491 journals)            First | 1 2 3 4 5 6 7 8 | Last

Showing 201 - 400 of 1720 Journals sorted alphabetically
Biological Research     Open Access   (Followers: 1)
Biological Rhythm Research     Hybrid Journal   (Followers: 1)
Biological Theory     Hybrid Journal   (Followers: 3)
Biological Trace Element Research     Hybrid Journal  
Biologicals     Full-text available via subscription   (Followers: 7)
Biologics: Targets & Therapy     Open Access   (Followers: 1)
Biologie Aujourd'hui     Full-text available via subscription  
Biologie in Unserer Zeit (Biuz)     Hybrid Journal   (Followers: 36)
Biologija     Open Access  
Biology     Open Access   (Followers: 3)
Biology and Philosophy     Hybrid Journal   (Followers: 18)
Biology Bulletin     Hybrid Journal   (Followers: 1)
Biology Bulletin Reviews     Hybrid Journal  
Biology Direct     Open Access   (Followers: 9)
Biology Letters     Full-text available via subscription   (Followers: 44)
Biology Methods and Protocols     Open Access  
Biology of Sex Differences     Open Access   (Followers: 1)
Biology of the Cell     Full-text available via subscription   (Followers: 9)
Biology Open     Open Access  
Biology, Medicine, & Natural Product Chemistry     Open Access   (Followers: 2)
Bioma : Jurnal Ilmiah Biologi     Open Access  
Biomacromolecules     Hybrid Journal   (Followers: 23)
Biomarker Insights     Open Access   (Followers: 2)
Biomarkers     Hybrid Journal   (Followers: 4)
Biomass and Bioenergy     Partially Free   (Followers: 8)
Biomaterials     Hybrid Journal   (Followers: 55)
Biomaterials Advances     Full-text available via subscription   (Followers: 20)
Biomath     Open Access  
Biomatter     Open Access  
Biomechanics and Modeling in Mechanobiology     Hybrid Journal   (Followers: 8)
Biomedical Chromatography     Hybrid Journal   (Followers: 6)
Biomedical Engineering     Hybrid Journal   (Followers: 11)
Biomedical Engineering and Computational Biology     Open Access   (Followers: 11)
BioMedical Engineering OnLine     Open Access   (Followers: 4)
Biomedical Engineering: Applications, Basis and Communications     Hybrid Journal   (Followers: 4)
Biomedical Journal     Open Access   (Followers: 5)
Biomedical Science and Engineering     Open Access   (Followers: 5)
Biomedical Signal Processing and Control     Hybrid Journal   (Followers: 9)
BioMetals     Hybrid Journal   (Followers: 1)
Biometrical Letters     Open Access  
Biometrics     Hybrid Journal   (Followers: 51)
Biometrika     Hybrid Journal   (Followers: 21)
Biomimetic Intelligence and Robotics     Open Access  
Biomolecular NMR Assignments     Hybrid Journal   (Followers: 3)
Biomolecules     Open Access   (Followers: 1)
BioNanoScience     Partially Free   (Followers: 3)
Bionature     Open Access   (Followers: 1)
Biopreservation and Biobanking     Hybrid Journal   (Followers: 2)
Bioprocess and Biosystems Engineering     Hybrid Journal   (Followers: 9)
Bioresource Technology     Partially Free   (Followers: 9)
BioRisk     Open Access   (Followers: 2)
Biosaintifika : Journal of Biology & Biology Education     Open Access  
BioScience     Hybrid Journal   (Followers: 27)
Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science     Hybrid Journal   (Followers: 3)
Biosemiotics     Hybrid Journal   (Followers: 1)
Biosensors     Open Access   (Followers: 3)
Biosensors and Bioelectronics     Hybrid Journal   (Followers: 27)
Biosensors and Bioelectronics : X     Open Access   (Followers: 2)
Bioseparation     Hybrid Journal   (Followers: 1)
Biosfer : Jurnal Biologi dan Pendidikan Biologi     Open Access  
Biosfer : Jurnal Tadris Biologi     Open Access  
BioSocieties     Hybrid Journal   (Followers: 3)
Biospecies     Open Access  
BIOspektrum     Hybrid Journal   (Followers: 5)
Biostatistics     Hybrid Journal   (Followers: 18)
Biosystematics and Ecology     Open Access   (Followers: 3)
Biosystems     Hybrid Journal   (Followers: 3)
Biosystems Diversity     Open Access  
Biota Amazônia     Open Access  
Biota Neotropica     Open Access  
Biotechnology Advances     Hybrid Journal   (Followers: 34)
Biotropia : The Southeast Asian Journal of Tropical Biology     Open Access  
Biotropica     Hybrid Journal   (Followers: 19)
Birth Defects Research     Hybrid Journal  
BJHM Open Research     Full-text available via subscription   (Followers: 1)
BMC Bioinformatics     Open Access   (Followers: 111)
BMC Biology     Open Access   (Followers: 50)
BMC Developmental Biology     Open Access   (Followers: 13)
BMC Evolutionary Biology     Open Access   (Followers: 58)
BMC Genomics     Open Access   (Followers: 69)
BMC Molecular and Cell Biology     Open Access   (Followers: 40)
BMC Proceedings     Full-text available via subscription   (Followers: 2)
BMC Research Notes     Open Access   (Followers: 3)
BMC Structural Biology     Open Access   (Followers: 8)
BMC Systems Biology     Open Access   (Followers: 16)
Boletín Científico : Centro de Museos. Museo de Historia Natural     Open Access  
Boletín del Centro de Investigaciones Biológicas     Open Access  
Boletín Micológico     Open Access  
Bone Reports     Open Access  
Bonorowo Wetlands     Open Access  
Borneo Journal of Resource Science and Technology     Open Access  
Bothalia : African Biodiversity & Conservation     Open Access  
Brain Science Advances     Open Access  
Brazilian Journal of Biological Sciences     Open Access  
Breastfeeding Medicine     Hybrid Journal   (Followers: 20)
Briefings in Bioinformatics     Hybrid Journal   (Followers: 43)
Briefings in Functional Genomics     Hybrid Journal   (Followers: 3)
British Poultry Abstracts     Hybrid Journal   (Followers: 3)
Brittonia     Hybrid Journal  
Bulletin de la Société Royale des Sciences de Liège     Open Access  
Bulletin of Experimental Biology and Medicine     Hybrid Journal  
Bulletin of Mathematical Biology     Hybrid Journal   (Followers: 9)
Bulletin of the Ecological Society of America     Open Access   (Followers: 4)
Bulletin of the Lebedev Physics Institute     Hybrid Journal  
Butlletí de la Institució Catalana d'Història Natural     Open Access  
CABI Agriculture and Bioscience     Open Access   (Followers: 1)
Caldasia     Open Access  
Cameroon Journal of Experimental Biology     Open Access  
Canadian Journal of Bioethics     Open Access  
Canadian Journal of Plant Pathology     Hybrid Journal   (Followers: 3)
Çanakkale Onsekiz Mart University Journal of Marine Sciences and Fisheries     Open Access  
Cancer Biology & Therapy     Open Access   (Followers: 11)
Cancer Cell International     Open Access   (Followers: 7)
Carbon Capture Science & Technology     Open Access  
Carbon Management     Hybrid Journal   (Followers: 5)
Carbon Resources Conversion     Open Access   (Followers: 2)
Caryologia : International Journal of Cytology, Cytosystematics and Cytogenetics     Partially Free  
Caucasiana     Open Access  
Cell     Full-text available via subscription   (Followers: 1146)
Cell Adhesion & Migration     Open Access   (Followers: 9)
Cell and Tissue Banking     Hybrid Journal   (Followers: 1)
Cell and Tissue Biology     Hybrid Journal   (Followers: 4)
Cell and Tissue Research     Hybrid Journal   (Followers: 5)
Cell Biochemistry and Function     Hybrid Journal   (Followers: 8)
Cell Biology and Development     Open Access   (Followers: 2)
Cell Biology and Toxicology     Hybrid Journal   (Followers: 10)
Cell Biology Education     Free   (Followers: 4)
Cell Biology International     Hybrid Journal   (Followers: 4)
Cell Biology International Reports     Hybrid Journal   (Followers: 2)
Cell Calcium     Hybrid Journal   (Followers: 2)
Cell Communication & Adhesion     Hybrid Journal   (Followers: 2)
Cell Cycle     Full-text available via subscription   (Followers: 5)
Cell Death and Differentiation     Hybrid Journal   (Followers: 7)
Cell Discovery     Open Access   (Followers: 2)
Cell Division     Open Access   (Followers: 1)
Cell Genomics     Full-text available via subscription   (Followers: 2)
Cell Metabolism     Full-text available via subscription   (Followers: 58)
Cell Proliferation     Open Access  
Cell Reports     Open Access   (Followers: 61)
Cell Reports Medicine     Open Access   (Followers: 3)
Cell Reports Methods     Open Access   (Followers: 1)
Cell Research     Hybrid Journal   (Followers: 11)
Cell Stress and Chaperones     Hybrid Journal   (Followers: 1)
Cell Surface     Open Access  
Cell Systems     Hybrid Journal   (Followers: 7)
Cells     Open Access   (Followers: 2)
Cells & Development     Hybrid Journal   (Followers: 3)
Cells Tissues Organs     Full-text available via subscription   (Followers: 1)
Cellular Immunology     Hybrid Journal   (Followers: 29)
Cellular Logistics     Full-text available via subscription  
Cellular Microbiology     Hybrid Journal   (Followers: 12)
Cellular Oncology     Hybrid Journal   (Followers: 3)
Cellular Reprogramming     Hybrid Journal  
Cellular Signalling     Hybrid Journal   (Followers: 10)
Ceylon Journal of Science     Open Access  
Channels     Open Access   (Followers: 1)
Check List : The Journal of Biodiversity Data     Open Access   (Followers: 2)
Chem     Hybrid Journal  
ChemBioEng Reviews     Full-text available via subscription   (Followers: 3)
Chemosensory Perception     Hybrid Journal  
Chirality     Hybrid Journal  
Chromosoma     Hybrid Journal  
Chromosome Research     Hybrid Journal   (Followers: 2)
Ciencia     Open Access  
Ciencia Amazónica (Iquitos)     Open Access  
Ciência ET Praxis     Open Access  
CienciaUAT     Open Access  
Cladistics     Hybrid Journal   (Followers: 7)
Climate Change Ecology     Open Access   (Followers: 16)
Clinical Dysmorphology     Hybrid Journal  
Clinical Phytoscience     Open Access  
Clinical Proteomics     Open Access   (Followers: 3)
Clinical Spectroscopy     Open Access   (Followers: 1)
Coevolution     Open Access  
Cogent Biology     Open Access  
Cognitive Neurodynamics     Hybrid Journal   (Followers: 2)
Cold Spring Harbor Perspectives in Biology     Full-text available via subscription   (Followers: 3)
Cold Spring Harbor Protocols     Full-text available via subscription   (Followers: 4)
Communication in Biomathematical Sciences     Open Access   (Followers: 2)
Communications Biology     Open Access  
Communications in Applied Sciences     Open Access  
Communications Materials     Open Access  
Communicative & Integrative Biology     Open Access  
Community Ecology     Full-text available via subscription   (Followers: 27)
Comparative Medicine     Full-text available via subscription   (Followers: 5)
Composite Interfaces     Hybrid Journal   (Followers: 6)
Comptes Rendus : Chimie     Open Access  
Comptes Rendus Biologies     Open Access   (Followers: 1)
Computational Biology Journal     Open Access   (Followers: 6)
Computational Mathematics and Mathematical Physics     Hybrid Journal   (Followers: 5)
Computer Methods in Biomechanics and Biomedical Engineering     Hybrid Journal   (Followers: 10)
Computer Methods in Biomechanics and Biomedical Engineering : Imaging & Visualization     Hybrid Journal  
Computers in Biology and Medicine     Hybrid Journal   (Followers: 11)
Connective Tissue Research     Hybrid Journal  
Contact (CTC)     Open Access  
Contributions to Plasma Physics     Hybrid Journal   (Followers: 3)
CRISPR Journal     Hybrid Journal  
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 19)
Crustaceana     Hybrid Journal   (Followers: 6)
Cryobiology     Hybrid Journal   (Followers: 3)

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Similar Journals
Journal Cover
Cell Biology and Toxicology
Journal Prestige (SJR): 0.924
Citation Impact (citeScore): 5
Number of Followers: 10  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1573-6822 - ISSN (Online) 0742-2091
Published by Springer-Verlag Homepage  [2469 journals]
  • CircZNF609 promotes bladder cancer progression and inhibits cisplatin
           sensitivity via miR-1200/CDC25B pathway

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      Abstract: Circular RNAs (circRNAs) have been extensively studied in tumor development and treatment. CircZNF609 (hsa_circ_0000615) has been shown to serve as an oncogene in all kinds of solid tumors and may act as the novel biomarker in tumor diagnosis and therapy in tumor early diagnosis and therapy. However, the underlying character and mechanism of circZNF609 in cisplatin chemosensitivity and bladder cancer (BCa) development were unknown. The expression level of cell division cycle 25B (CDC25B), microRNA 1200 (miR-1200), and circZNF609 in BCa cells and tissues depended on quantitative real-time PCR (qRT-PCR). CDC25B protein level was assayed with Western blot. Functional assays in vitro and in vivo had been conducted to inspect the important role of circZNF609 on BCa progression and cisplatin chemosensitivity in BCa. RNA sequencing and online databases were used to predict the interactions among circZNF609, miR-1200, and CDC25B. Mechanistic exploration was confirmed by RNA pull-down assay, RNA fluorescence in situ hybridization (FISH) and Dual luciferase reporter assay. CircZNF609 expression was increased significantly in BCa cell lines and tissues. For BCa patients, increased expression of circZNF609 was correlated with a worse survival. In vitro and in vivo, enforced expression of circZNF609 enhanced BCa cells proliferation, migration, and cisplatin chemoresistance. Mechanistically, circZNF609 alleviated the inhibition effect on target CDC25B expression by sponging miR-1200. CircZNF609 promoted tumor growth through novel circZNF609/miR-1200/CDC25B axis, implying that circZNF609 has significant potential to act as a new diagnostic biomarker and therapeutic target in BCa. Graphical abstract Enhancing cisplatin sensitivity is an important direction for bladder cancer management. 1. This research reveals that circZNF609 improves bladder cancer progression and inhibits cisplatin sensitivity by inducing G1/S cell cycle arrest via a novel miR-1200/CDC25B cascades. 2. CircZNF609 was confirmed associated with worse survival of bladder cancer patients. 3. CircZNF609 act as a prognostic biomarker for bladder cancer treatment.
      PubDate: 2022-05-14
       
  • Urine-derived stem cells-extracellular vesicles ameliorate diabetic
           osteoporosis through HDAC4/HIF-1α/VEGFA axis by delivering
           microRNA-26a-5p

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      Abstract: Critical roles of stem cell-extracellular vesicles (EVs) in the management of osteoporosis have been documented. Here, this study was designed to enlarge the research of the specific effects and underlying mechanism of urine-derived stem cells-EVs (USCs-EVs) on osteoporosis in diabetes rats. Firstly, miR-26a-5p and histone deacetylase 4 (HDAC4) expression in USCs of rats after diabetic osteoporosis (DOP) modeling induced by streptozotocin injection was determined, followed by study of their interaction. Then, USCs-EVs were co-cultured with osteogenic precursor cells, the effects of miRNA-26a-5p (miR-26a-5p) on osteoblasts, osteoclasts, bone mineralization deposition rate were evaluated. Meanwhile, the effect of USCs-EVs carrying miR-26a-5p on DOP rats was assessed. Elevated miR-26a-5p was seen in USCs-EVs which limited HDAC4 expression. Moreover, USCs-EVs delivered miR-26a-5p to osteogenic precursor cells, thereby promoting their differentiation, enhancing the activity of osteoblasts, and inhibiting the activity of osteoclasts, thereby preventing DOP through the activation of hypoxia inducible factor 1 subunit alpha (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway by repressing HDAC4. In a word, USCs-EVs-miR-26a-5p is a promising therapy for DOP by activating HIF-1α/VEGFA pathway through HDAC4 inhibition. Graphical abstract 1. USCs-EVs-miR-26a-5p targeted HDAC4 and limited HDAC4 expression. 2. miR-26a-5p was delivered by USCs-EVs into osteoblast precursor cells. 3. USCs-EVs-miR-26a-5p promoted the differentiation of osteoblast precursor cells into osteoblasts. 4. miR-26a-5p delivered by USCs-EVs could inhibit HDAC4. 5. USCs-EVs-miR-26a-5p could prevent the pathogenesis of DOP via HIF-1α/VEGFA aix.
      PubDate: 2022-05-13
       
  • High-content high-throughput imaging reveals distinct connections between
           mitochondrial morphology and functionality for OXPHOS complex I, III, and
           V inhibitors

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      Abstract: Abstract Cells can adjust their mitochondrial morphology by altering the balance between mitochondrial fission and fusion to adapt to stressful conditions. The connection between a chemical perturbation, changes in mitochondrial function, and altered mitochondrial morphology is not well understood. Here, we made use of high-throughput high-content confocal microscopy to assess the effects of distinct classes of oxidative phosphorylation (OXPHOS) complex inhibitors on mitochondrial parameters in a concentration and time resolved manner. Mitochondrial morphology phenotypes were clustered based on machine learning algorithms and mitochondrial integrity patterns were mapped. In parallel, changes in mitochondrial membrane potential (MMP), mitochondrial and cellular ATP levels, and viability were microscopically assessed. We found that inhibition of MMP, mitochondrial ATP production, and oxygen consumption rate (OCR) using sublethal concentrations of complex I and III inhibitors did not trigger mitochondrial fragmentation. Instead, complex V inhibitors that suppressed ATP and OCR but increased MMP provoked a more fragmented mitochondrial morphology. In agreement, complex V but not complex I or III inhibitors triggered proteolytic cleavage of the mitochondrial fusion protein, OPA1. The relation between increased MMP and fragmentation did not extend beyond OXPHOS complex inhibitors: increasing MMP by blocking the mPTP pore did not lead to OPA1 cleavage or mitochondrial fragmentation and the OXPHOS uncoupler FCCP was associated with OPA1 cleavage and MMP reduction. Altogether, our findings connect vital mitochondrial functions and phenotypes in a high-throughput high-content confocal microscopy approach that help understanding of chemical-induced toxicity caused by OXPHOS complex perturbing chemicals.
      PubDate: 2022-05-04
       
  • hMSCs-derived exosome circCDK13 inhibits liver fibrosis by regulating the
           expression of MFGE8 through miR-17-5p/KAT2B

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      Abstract: Objective To investigate the effects of human bone marrow mesenchymal stem cells (hMSCs)-derived exosome circCDK13 on liver fibrosis and its mechanism. Methods Exosomes derived from hMSCs were extracted and identified by flow cytometry and osteogenic and adipogenic induction, and the expressions of marker proteins on the surface of exosomes were detected by western blot. Cell proliferation was measured by CCK8 assay, the expression of active markers of HSCs by immunofluorescence, and the expressions of fibrosis-related factors by western blot. A mouse model of liver fibrosis was established by intraperitoneal injection of thioacetamide (TAA). Fibrosis was detected by HE staining, Masson staining, and Sirius red staining. Western blot was utilized to test the expressions of PI3K/AKT and NF-κB pathway related proteins, dual-luciferase reporter assay and RIP assay to validate the binding between circCDK13 and miR-17-5p as well as between miR-17-5p and KAT2B, and ChIP to validate the effect of KAT2B on H3 acetylation and MFGE8 transcription. Results hMSCs-derived exosomes inhibited liver fibrosis mainly through circCDK13. Dual-luciferase reporter assay and RIP assay demonstrated the binding between circCDK13 and miR-17-5p as well as between miR-17-5p and KAT2B. Further experimental results indicated that circCDK13 mediated liver fibrosis by regulating the miR-17-5p/KAT2B axis, and KAT2B promoted MFGE8 transcription by H3 acetylation. Exo-circCDK13 inhibited PI3K/AKT and NF-κB signaling pathways activation through regulating the miR-17-5p/KAT2B axis. Conclusion hMSCs-derived exosome circCDK13 inhibited liver fibrosis by regulating the expression of MFGE8 through miR-17-5p/KAT2B axis. Graphical abstract
      PubDate: 2022-04-29
       
  • Alleviative effect of microRNA-497 on diabetic neuropathic pain in rats in
           relation to decreased USP15

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      Abstract: The current study tries to discuss the functional role of microRNA-497 (miR-497) in diabetic neuropathic pain (DNP) and the related downstream mechanism. Bioinformatics analysis was implemented for the identification of differentially expressed miRNAs and genes. DNP was simulated in rats through intraperitoneal injection of streptozotocin. The expression patterns of miR-497, USP15, NRF2, and G6PD were then determined. The binding of miR-497 and USP15 was confirmed. Using gain- and loss-of-function assays, we analyzed the critical role of miR-497-mediated USP15 in DNP through the NRF2/G6PD axis. Downregulated miR-497 and elevated USP15 were observed in the dorsal root ganglion neurons isolated from spinal cord tissues of STZ-induced DNP rats. miR-497 could alleviate DNP, which was associated with suppression of USP15, a confirmed target of miR-497. USP15 enhanced the degradation and ubiquitination of NRF2 and induced G6PD expression, leading to the progression of DNP. We highlighted the crucial role of miR-497-mediated USP15 in DNP through the NRF2/G6PD axis. Graphical abstract 1. miR-497 is downregulated in DRG neurons from spinal cord tissues of STZ-induced DNP rats. 2. miR-497 inhibits the expression of USP15, thereby alleviating STZ-induced DNP in rats. 3. USP15 promotes ubiquitination and degradation of NRF2, reducing the expression of G6PD. 4. miR-497 alleviates STZ-induced DNP in rats by regulating the USP15/NRF2/G6PD axis.
      PubDate: 2022-04-27
       
  • YY1 inactivated transcription co-regulator PGC-1α to promote
           mitochondrial dysfunction of early diabetic nephropathy-associated
           tubulointerstitial fibrosis

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      Abstract: Abstract The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which had a closely relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) played an important role not only in regulating fibrosis process, but also in maintaining mitochondrial function of pancreatic β cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG upregulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose cultured HK-2 cells and 8-week-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF .
      PubDate: 2022-04-21
       
  • Deubiquitinase USP19 enhances phenylalanine hydroxylase protein stability
           and its enzymatic activity

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      Abstract: Phenylalanine hydroxylase (PAH) is the key enzyme in phenylalanine metabolism, deficiency of which is associated with the most common metabolic phenotype of phenylketonuria (PKU) and hyperphenylalaninemia (HPA). A bulk of PKU disease-associated missense mutations in the PAH gene have been studied, and the consequence of each PAH variant vary immensely. Prior research established that PKU-associated variants possess defects in protein folding with reduced cellular stability leading to rapid degradation. However, recent evidence revealed that PAH tetramers exist as a mixture of resting state and activated state whose transition depends upon the phenylalanine concentration and certain PAH variants that fail to modulate the structural equilibrium are associated with PKU disease. Collectively, these findings framed our understanding of the complex genotype–phenotype correlation in PKU. In the current study, we substantiate a link between PAH protein stability and its degradation by the ubiquitin-mediated proteasomal degradation system. Here, we provide an evidence that PAH protein undergoes ubiquitination and proteasomal degradation, which can be reversed by deubiquitinating enzymes (DUBs). We identified USP19 as a novel DUB that regulates PAH protein stability. We found that ectopic expression of USP19 increased PAH protein level, whereas depletion of USP19 promoted PAH protein degradation. Our study indicates that USP19 interacts with PAH and prevents polyubiquitination of PAH subsequently extending the half-life of PAH protein. Finally, the increase in the level of PAH protein by the deubiquitinating activity of USP19 resulted in enhanced metabolic function of PAH. In summary, our study identifies the role of USP19 in regulating PAH protein stability and promotes its metabolic activity. Graphical abstract Graphical highlights 1. E3 ligase Cdh1 promotes PAH protein degradation leading to insufficient cellular amount of PAH causing PKU. 2. A balance between E3 ligase and DUB is important to regulate the proteostasis of PAH. 3. USP19 deubiquitinates and stabilizes PAH further protecting it from rapid degradation. 4. USP19 increases the enzymatic activity of PAH, thus maintaining normal Phe levels.
      PubDate: 2022-04-21
       
  • Lipopolysaccharide facilitates immune escape of hepatocellular carcinoma
           cells via m6A modification of lncRNA MIR155HG to upregulate PD-L1
           expression

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      Abstract: Recent studies have suggested that the initiation and progression of hepatocellular carcinoma (HCC) are closely associated with lipopolysaccharide (LPS) of intestinal bacteria. However, the role of LPS in immune regulation of HCC remains largely unknown. An orthotopic Hepa1-6 tumor model of HCC was constructed to analyze the effect of LPS on the expression of immune checkpoint molecules PD-1 and PD-L1. Then we verified the regulation of PD-L1 by LPS in HCC cells. Based on the previous finding that lncRNA MIR155HG regulates PD-L1 expression in HCC cells, we analyzed the relationship of LPS signaling pathway molecules with PD-L1 and MIR155HG by bioinformatics. The molecular mechanism of MIR155HG regulating PD-L1 expression induced by LPS was investigated by RNA pull-down followed by mass spectrometry, RNA immunoprecipitation, fluorescence in situ hybridization, and luciferase reporter assay. Finally, the HepG2 xenograft model was established to determine the role of MIR155HG on PD-L1 expression in vivo. We showed that LPS induced PD-1 and PD-L1 expression in mouse tumor tissues and induced PD-L1 expression in HCC cells. Mechanistically, upregulation of METTL14 by LPS promotes the m6A methylation of MIR155HG, which stabilizes MIR155HG relying on the “reader” protein ELAVL1 (also known as HuR)-dependent pathway. Moreover, MIR155HG functions as a competing endogenous RNA (ceRNA) to modulate the expression of PD-L1 by miR-223/STAT1 axis. Our results suggested that LPS plays a critical role in immune escape of HCC through METTL14/MIR155HG/PD-L1 axis. This study provides a new insight for understanding the complex immune microenvironment of HCC. Graphical abstract 1. LPS plays a critical role in immune escape of HCC, especially HCC with cirrhosis. 2. Our study reveals that LPS regulates PD-L1 by m6A modification of lncRNA in HCC. 3. MIR155HG plays an important role in LPS induced PD-L1 expression. 4. LPS-MIR155HG-PD-L1 regulatory axis provides a new target for the treatment of HCC.
      PubDate: 2022-04-19
       
  • Transcriptomic analysis in zebrafish larvae identifies iron-dependent
           mitochondrial dysfunction as a possible key event of NAFLD progression
           induced by benzo[a]pyrene/ethanol co-exposure

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      Abstract: Non-alcoholic fatty liver disease (NAFLD) is a worldwide epidemic for which environmental contaminants are increasingly recognized as important etiological factors. Among them, the combination of benzo[a]pyrene (B[a]P), a potent environmental carcinogen, with ethanol, was shown to induce the transition of steatosis toward steatohepatitis. However, the underlying mechanisms involved remain to be deciphered. In this context, we used high-fat diet fed zebrafish model, in which we previously observed progression of steatosis to a steatohepatitis-like state following a 7-day-co-exposure to 43 mM ethanol and 25 nM B[a]P. Transcriptomic analysis highlighted the potent role of mitochondrial dysfunction, alterations in heme and iron homeostasis, involvement of aryl hydrocarbon receptor (AhR) signaling, and oxidative stress. Most of these mRNA dysregulations were validated by RT-qPCR. Moreover, similar changes were observed using a human in vitro hepatocyte model, HepaRG cells. The mitochondria structural and functional alterations were confirmed by transmission electronic microscopy and Seahorse technology, respectively. Involvement of AhR signaling was evidenced by using in vivo an AhR antagonist, CH223191, and in vitro in AhR-knock-out HepaRG cells. Furthermore, as co-exposure was found to increase the levels of both heme and hemin, we investigated if mitochondrial iron could induce oxidative stress. We found that mitochondrial labile iron content was raised in toxicant-exposed larvae. This increase was prevented by the iron chelator, deferoxamine, which also inhibited liver co-exposure toxicity. Overall, these results suggest that the increase in mitochondrial iron content induced by B[a]P/ethanol co-exposure causes mitochondrial dysfunction that contributes to the pathological progression of NAFLD. Graphical abstract
      PubDate: 2022-04-12
       
  • 27-Hydroxycholesterol is a specific factor in the neoplastic
           microenvironment of HCC that causes MDR via GRP75 regulation of the redox
           balance and metabolic reprogramming

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      Abstract: Objective Due to the tissue specificity of the liver, long-term exposure to a high concentration of 27-hydroxycholesterol (27HC) is a special characteristic of the tumour microenvironment in hepatocellular carcinoma (HCC). However, what occurs after HCC cells are long-term exposure to 27HC and the molecular mechanisms involved remain largely unexamined. Methods A long-term 27HC-treated HepG2 cell line and the xenografts in nude mice were used as experimental models. Molecular mechanisms were investigated using bioinformatics analysis and molecular biological experiments. Results Here, we found that by inducing an increase in oxidative stress signalling, 27HC activated glucose-regulated protein 75 (GRP75). On the one hand, GRP75 resulted in a change in the redox balance by regulating ROS generation and antioxidant system activity via affecting MMP, NRF2, HO-1, and NQO1 levels. On the other hand, GRP75 modified the metabolic reprogramming process by regulating key factors (HIF-1α, p-Akt, and c-myc) and glucose uptake, facilitating HCC cell growth in the inhospitable microenvironment. These two factors caused HCC cells to resist 27HC-induced cytotoxicity and attain multidrug resistance (MDR). Conclusions Our present study not only identified 27HC, a characteristic component of the neoplastic microenvironment of HCC that causes MDR via GRP75 to regulate the redox balance and metabolic reprogramming, but also revealed that targeted intervention by the “switch”-like molecule GRP75 could reverse the effect of 27HC from cancer promotion to cytotoxicity in HCC, suggesting a new strategy for specific intervention of HCC.
      PubDate: 2022-04-01
       
  • Metastatic suppression by DOC2B is mediated by inhibition of
           epithelial-mesenchymal transition and induction of senescence

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      Abstract: Senescence induction and epithelial-mesenchymal transition (EMT) events are the opposite sides of the spectrum of cancer phenotypes. The key molecules involved in these processes may get influenced or altered by genetic and epigenetic changes during tumor progression. Double C2-like domain beta (DOC2B), an intracellular vesicle trafficking protein of the double C2 protein family, plays a critical role in exocytosis, neurotransmitter release, and intracellular vesicle trafficking. DOC2B is repressed by DNA promoter hypermethylation and functions as a tumor growth regulator in cervical cancer. To date, the molecular mechanisms of DOC2B in cervical cancer progression and metastasis is elusive. Herein, the biological functions and molecular mechanisms regulated by DOC2B and its impact on senescence and EMT are described. DOC2B inhibition promotes proliferation, growth, and migration by relieving G0/G1-S arrest, actin remodeling, and anoikis resistance in Cal27 cells. It enhanced tumor growth and liver metastasis in nude mice with the concomitant increase in metastasis-associated CD55 and CD61 expression. Inhibition of EMT and promotion of senescence by DOC2B is a calcium-dependent process and accompanied by calcium-mediated interaction between DOC2B and CDH1. In addition, we have identified several EMT and senescence regulators as targets of DOC2B. We show that DOC2B may act as a metastatic suppressor by inhibiting EMT through induction of senescence via DOC2B-calcium-EMT-senescence axis. Graphical abstract
      PubDate: 2022-04-01
       
  • Stanniocalcin-2 promotes cell EMT and glycolysis via activating
           ITGB2/FAK/SOX6 signaling pathway in nasopharyngeal carcinoma

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      Abstract: Abstract Stanniocalcin-2 (STC2) has been proved to regulate a variety of signaling pathways including cell growth, metastasis, and therapeutic resistance. However, the role of STC2 in the regulation of nasopharyngeal carcinoma (NPC) remains poorly understood. In this study, we investigated the regulatory function of STC2 on epithelial-mesenchymal transition (EMT) and glycolysis traits in NPC and revealed the underlying molecular mechanisms. We found that STC2 was highly expressed in primary nasopharyngeal carcinoma tissues and lymph node metastatic tissues. Silencing of STC2 inhibited cell proliferation, invasion, and glycolysis. Further analyses for the clinical samples demonstrated that STC2 expression was associated with the poor clinical progression. Moreover, we demonstrated the interaction of ITGB2 with STC2 and its involvement in STC2-mediated ITGB2/FAK/SOX6 axis. Collectively, our results provide new insights into understanding the regulatory mechanism of STC2 and suggest that the STC2/ITGB2/FAK/SOX6 signaling axis may be a potential therapeutic target for NPC.
      PubDate: 2022-04-01
       
  • Interleukin-17A mediates tobacco smoke–induced lung cancer
           epithelial-mesenchymal transition through transcriptional regulation of
           ΔNp63α on miR-19

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      Abstract: Interleukin-17A (IL-17A) is an essential inflammatory cytokine in the progress of carcinogenesis. Tobacco smoke (TS) is a major risk factor of lung cancer that influences epithelial-mesenchymal transition (EMT) process. However, the potential mechanism by which IL-17A mediates the progression of lung cancer in TS-induced EMT remains elusive. In the present study, it was revealed that the IL-17A level was elevated in lung cancer tissues, especially in tumor tissues of cases with experience of smoking, and a higher IL-17A level was correlated with induction of EMT in those specimens. Moreover, the expression of ΔNp63α was increased in IL-17A-stimulated lung cancer cells. ΔNp63α functioned as a key oncogene that bound to the miR-17-92 cluster promoter and transcriptionally increased the expression of miR-19 in lung cancer cells. Overexpression of miR-19 promoted EMT in lung cancer with downregulation of E-cadherin and upregulation of N-cadherin, while its inhibition suppressed EMT. Finally, the upregulated levels of IL-17A, ΔNp63α, and miR-19 along with the alteration of EMT-associated biomarkers were found in lung tissues of TS-exposed mice. Taken together, the abovementioned results suggest that IL-17A increases ΔNp63α expression, transcriptionally elevates miR-19 expression, and promotes TS-induced EMT in lung cancer. These findings may provide a new insight for the identification of therapeutic targets for lung cancer. Graphical abstract
      PubDate: 2022-04-01
       
  • Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor
           and cognitive deficits

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      Abstract: Clinical surgical practices have found that children who undergo multiple anesthesia may have an increased risk of deficiencies in cognition and fine motor control. Here, we report that YT521-B homology domain family 1 (YTHDF1), a critical reader protein for N6-methyladenosine-modified mRNA, was significantly downregulated in the prefrontal cortex of young mice after multiple sevoflurane anesthesia exposures. Importantly, sevoflurane led to a decrease in protein synthesis in mouse cortical neurons that was fully rescued by YTHDF1, suggesting that anesthesia may affect early brain development by affecting m6A-dependent mRNA translation. Transcriptome-wide experiments showed that numerous mRNA targets related to synaptic functions in the prefrontal mouse cortex were associated with m6A methylation and YTHDF1. In particular, we found that synaptophysin, a critical presynaptic protein, was specifically modified by m6A methylation and associated with YTHDF1, and m6A methylation of synaptophysin decreased with multiple sevoflurane exposures. Importantly, we showed that fine motor control skills and cognitive functions were impaired in mice with multiple anesthesia exposures, and these effects were fully reversed by reintroducing YTHDF1 through a blood-brain barrier (BBB)-crossing viral delivery system. Finally, we found that the fine motor skills in children who underwent prolonged anesthesia were compromised 6 months after surgery. Our findings indicated that impairment in the translational regulation of mRNA via N6-methyladenosine methylation is a potential mechanism underlying the effects of anesthesia on neural development in the young brain. Graphical abstract 1. N6-methyladenosine (m6A) modifications were involved in anesthesia-induced neurotoxicity. 2. Sevoflurane impairs m6A-mediated mRNA translation and leads to fine motor deficits in young mice. 3. YTHDF1, a m6A reader protein, rescued sevoflurane-induced protein synthesis inhibition and fine motor deficits in young mice.
      PubDate: 2022-04-01
       
  • Pyrrolizidine alkaloids cause cell cycle and DNA damage repair defects as
           analyzed by transcriptomics in cytochrome P450 3A4-overexpressing HepG2
           clone 9 cells

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      Abstract: Pyrrolizidine alkaloids (PAs) are a large group of highly toxic chemical compounds, which are found as cross-contaminants in numerous food products (e.g., honey), dietary supplements, herbal teas, and pharmaceutical herbal medicines. PA contaminations are responsible for serious hepatotoxicity and hepatocarcinogenesis. Health authorities have to set legal limit values to guarantee the safe consumption of plant-based nutritional and medical products without harmful health. Toxicological and chemical analytical methods are conventionally applied to determine legally permitted limit values for PAs. In the present investigation, we applied a highly sensitive transcriptomic approach to investigate the effect of low concentrations of five PAs (lasiocarpine, riddelliine, lycopsamine, echimidine, and monocrotaline) on human cytochrome P450 3A4-overexpressing HepG2 clone 9 hepatocytes. The transcriptomic profiling of deregulated gene expression indicated that the PAs disrupted important signaling pathways related to cell cycle regulation and DNA damage repair in the transfected hepatocytes, which may explain the carcinogenic PA effects. As PAs affected the expression of genes that involved in cell cycle regulation, we applied flow cytometric cell cycle analyses to verify the transcriptomic data. Interestingly, PA treatment led to an arrest in the S phase of the cell cycle, and this effect was more pronounced with more toxic PAs (i.e., lasiocarpine and riddelliine) than with the less toxic monocrotaline. Using immunofluorescence, high fractions of cells were detected with chromosome congression defects upon PA treatment, indicating mitotic failure. In conclusion, the tested PAs revealed threshold concentrations, above which crucial signaling pathways were deregulated resulting in cell damage and carcinogenesis. Cell cycle arrest and DNA damage repair point to the mutagenicity of PAs. The disturbance of chromosome congression is a novel mechanism of Pas, which may also contribute to PA-mediated carcinogenesis. Transcriptomic, cell cycle, and immunofluorescence analyses should supplement the standard techniques in toxicology to unravel the biological effects of PA exposure in liver cells as the primary target during metabolization of PAs. Graphical abstract
      PubDate: 2022-04-01
       
  • Lnc-HZ08 regulates BPDE-induced trophoblast cell dysfunctions by promoting
           PI3K ubiquitin degradation and is associated with miscarriage

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      Abstract: Increasing evidences have shown that pregnant women might miscarry after exposure with environmental BaP (benzo(a)pyrene). Additionally, BPDE (benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide), the ultimate metabolite of BaP, could induce dysfunctions of human trophoblast cells. However, it is rarely correlated between miscarriage and trophoblast dysfunctions. Moreover, their underlying mechanisms are still largely unidentified. In this study, a novel lncRNA (long non-coding RNA), lnc-HZ08, was identified to be highly expressed in human recurrent miscarriage (RM) tissues and in BPDE-treated human trophoblast cells. Lnc-HZ08 acts as a RNA scaffold to interact with both PI3K and its ubiquitin ligase CBL (Cbl proto-oncogene), enhances their protein interactions, and promotes PI3K ubiquitin degradation. In RM tissues and BPDE-treated trophoblast cells, DNA methylation level in lnc-HZ08 promoter region was reduced, which promotes estrogen receptor 1 (ER)–mediated lnc-HZ08 transcription. Subsequently, this upregulated lnc-HZ08 downregulated PI3K level, suppressed PI3K/p-AKT/p-P21/CDK2 pathway, and thus weakened proliferation, migration, and invasion of human trophoblast cells, which further induces miscarriage. These results may provide novel scientific and clinical insights in the occurrence of unexplained miscarriage. Graphical abstract A novel lncRNA (lnc-HZ08) regulates the functions of human trophoblast cells and affects miscarriage. Lnc-HZ08 promotes PI3K ubiquitin degradation by enhancing CBL and PI3K interactions, downregulates PI3K/p-AKT/p-P21/CDK2 pathway, and weakens proliferation, migration, and invasion of trophoblast cells. BPDE exposure reduces the DNA methylation level in lnc-HZ08 promoter region and promotes estrogen receptor 1 (ER)–mediated lnc-HZ08 transcription. The suppressed PI3K/p-AKT/p-P21/CDK2 pathway regulated by increased lnc-HZ08 is associated with miscarriage. These results provide novel insights in the occurrence of unexplained miscarriage. Graphical Headlights • Lnc-HZ08 downregulates PI3K/p-AKT/p-P21/CDK2 pathway to suppress proliferation, migration, and invasion of human trophoblast cells, and affects miscarriage. • Lnc-HZ08 acts as a RNA scaffold to enhance the protein interaction of PI3K and its ubiquitin ligase CBL, which increases PI3K ubiquitination and degradation. • Lnc-HZ08 transcription is associated with DNA methylation on its promoter region and transcription factor ER.
      PubDate: 2022-04-01
       
  • Dimethyl sulfoxide stimulates the AhR-Jdp2 axis to control ROS
           accumulation in mouse embryonic fibroblasts

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      Abstract: The aryl hydrocarbon receptor (AhR) is a ligand-binding protein that responds to environmental aromatic hydrocarbons and stimulates the transcription of downstream phase I enzyme–related genes by binding the cis element of dioxin-responsive elements (DREs)/xenobiotic-responsive elements. Dimethyl sulfoxide (DMSO) is a well-known organic solvent that is often used to dissolve phase I reagents in toxicology and oxidative stress research experiments. In the current study, we discovered that 0.1% DMSO significantly induced the activation of the AhR promoter via DREs and produced reactive oxygen species, which induced apoptosis in mouse embryonic fibroblasts (MEFs). Moreover, Jun dimerization protein 2 (Jdp2) was found to be required for activation of the AhR promoter in response to DMSO. Coimmunoprecipitation and chromatin immunoprecipitation studies demonstrated that the phase I–dependent transcription factors, AhR and the AhR nuclear translocator, and phase II–dependent transcription factors such as nuclear factor (erythroid-derived 2)–like 2 (Nrf2) integrated into DRE sites together with Jdp2 to form an activation complex to increase AhR promoter activity in response to DMSO in MEFs. Our findings provide evidence for the functional role of Jdp2 in controlling the AhR gene via Nrf2 and provide insights into how Jdp2 contributes to the regulation of ROS production and the cell spreading and apoptosis produced by the ligand DMSO in MEFs. Graphical abstract
      PubDate: 2022-04-01
       
  • LINC02308 promotes the progression of glioma through activating
           mTOR/AKT-signaling pathway by targeting miR-30e-3p/TM4SF1 axis

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      Abstract: Background Glioma is a common brain malignancy, and the purpose of this study is to investigate the function of LINC02308 in glioma. Methods The differentially expressed lncRNAs were screened by microarray. The expression of LINC02308 in glioma tissues and cells was evaluated. The interaction among LINC02308, miR-30e-3p, and TM4SF1 was determined. Cell proliferation and apoptosis were evaluated. The expression of mTOR/AKT-signaling and apoptosis-related markers was detected by Western blot. A xenograft tumor mouse model was constructed to investigate the roles of LINC02308. Results LINC02308 was significantly overexpressed in glioma, and a high LINC02308 level was correlated with a poor prognosis. LINC02308 silencing markedly inhibited proliferation and reduced apoptosis of glioma cells and also suppressed tumor growth in the xenograft tumor mouse model. Finally, we demonstrated that LINC02308 played its oncogenic role through binding to miR-30e-3p so as to relieve miR-30e-3p-induced suppression of TM4SF1. Conclusions LINC02308 promoted glioma tumorigenesis as a sponge of miR-30e-3p to upregulate TM4SF1 and activate AKT/mTOR pathway. Graphical Hypothesis diagram illustrates the function and mechanism of LINC02308 in glioma. A schematic representation of the functional mechanism of LINC02308 in glioma.
      PubDate: 2022-04-01
       
  • Mechanistic understanding of the toxic effects of arsenic and warfare
           arsenicals on human health and environment

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      Abstract: Worldwide, more than 200 million people are estimated to be exposed to unsafe levels of arsenic. Chronic exposure to unsafe levels of groundwater arsenic is responsible for multiple human disorders, including dermal, cardiovascular, neurological, pulmonary, renal, and metabolic conditions. Consumption of rice and seafood (where high levels of arsenic are accumulated) is also responsible for human exposure to arsenic. The toxicity of arsenic compounds varies greatly and may depend on their chemical form, solubility, and concentration. Surprisingly, synthetic organoarsenicals are extremely toxic molecules which created interest in their development as chemical warfare agents (CWAs) during World War I (WWI). Among these CWAs, adamsite, Clark I, Clark II, and lewisite are of critical importance, as stockpiles of these agents still exist worldwide. In addition, unused WWII weaponized arsenicals discarded in water bodies or buried in many parts of the world continue to pose a serious threat to the environment and human health. Metabolic inhibition, oxidative stress, genotoxicity, and epigenetic alterations including micro-RNA-dependent regulation are some of the underlying mechanisms of arsenic toxicity. Mechanistic understanding of the toxicity of organoarsenicals is also critical for the development of effective therapeutic interventions. This review provides comprehensive details and a critical assessment of recently published data on various chemical forms of arsenic, their exposure, and implications on human and environmental health. Graphical abstract
      PubDate: 2022-04-01
       
  • LncRNA TUG1 compromised neuronal mitophagy in cerebral
           ischemia/reperfusion injury by targeting sirtuin 1

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      Abstract: Background Mitophagy protects against cerebral ischemia/reperfusion (CI/R)–induced neuronal apoptosis via mitochondrial clearance. Although taurine-upregulated gene 1 (lncRNA TUG1) has been proposed to be involved in the neuronal apoptosis evoked by CI/R, its specific role in mitophagy during the progression of CI/R injury remains unknown. Methods The CI/R rat model was established using middle cerebral artery occlusion/reperfusion (MCAO/R). Human neuroblastoma cell line SH-SY5Y was subjected to oxygen-glucose deprivation and reoxygenation (OGD/R). Ubiquitination assay, co-immunoprecipitation assay, RNA pull-down, and RNA immunoprecipitation were used to determine the interplay among TUG1, sirtuin 1 (SIRT1), and F-box and WD repeat domain-containing 7 (FBXW7). Results The upregulation of the TUG1 level and downregulation of the mitophagy were observed in both MCAO/R-treated rats and OGD/R-treated cells. The administration of si-TUG1 (a siRNA directed against TUG1) potentiated mitophagy and suppressed neuronal apoptosis in OGD/R-treated cells. However, the neuroprotective effect of si-TUG1 was reversed by mitophagy inhibitor or SIRT1 knockdown in vitro. Functionally, TUG1 enhanced FBXW7-mediated SIRT1 ubiquitination by upregulating FBXW7 expression. The overexpression of FBXW7 abrogated the si-TUG1-reinforced mitophagy by decreasing SIRT1 expression, thus aggravating neuronal apoptosis in the OGD/R+si-TUG1-treated cells. In rats with MCAO/R, the interference of TUG1 clearly decreased neuronal apoptosis, lessened the infarct volume, and relieved the neurological deficits. Conclusion TUG1 knockdown promotes SIRT1-induced mitophagy by suppressing FBXW7-mediated SIRT1 degradation, thus relieving the neuronal apoptosis induced by CI/R injury. Graphical abstract LncRNA TUG1 promotes neuronal apoptosis through inhibition of mitophagy. TUG1 decreased SIRT1 expression by promoting FBXW7-mediated SIRT1 ubiquitination. FBXW7/SIRT1 axis mediated the effect of TUG1 on OGD/R-induced neuronal apoptosis by regulating mitophagy.
      PubDate: 2022-03-28
       
 
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