Redox Factor-1 Activates Endothelial SIRTUIN1 through Reduction of Conserved Cysteine Sulfhydryls in Its Deacetylase Domain
| العنوان: | Redox Factor-1 Activates Endothelial SIRTUIN1 through Reduction of Conserved Cysteine Sulfhydryls in Its Deacetylase Domain |
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| المؤلفون: | Saet-Byel Jung, Kaikobad Irani, Santosh Kumar, Ajay Kumar, Asma Naqvi, Young-Rae Kim, Tohru Yamamori, Cuk-Seong Kim |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 6, p e65415 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Male, Anatomy and Physiology, endocrine system diseases, lcsh:Medicine, Cardiovascular, Cardiovascular System, Biochemistry, environment and public health, Tissue Culture Techniques, Redox Signaling, Mice, chemistry.chemical_compound, Sirtuin 1, Enos, Molecular Cell Biology, DNA-(Apurinic or Apyrimidinic Site) Lyase, Signaling in Cellular Processes, lcsh:Science, Aorta, Multidisciplinary, biology, Enzyme Classes, Chemistry, Nitric Oxide Synthase Type III, Acetylation, Neurochemistry, Enzymes, Vasodilation, Diffusion Chambers, Culture, Medicine, lipids (amino acids, peptides, and proteins), Neurochemicals, Oxidoreductases, Oxidation-Reduction, hormones, hormone substitutes, and hormone antagonists, Signal Transduction, Research Article, Deacetylase activity, Cell Physiology, Mice, Transgenic, Nitric Oxide, Nitric oxide, Enzyme Regulation, Enzyme activator, Vascular Biology, Animals, Humans, Cysteine, Biology, lcsh:R, biology.organism_classification, Enzyme Activation, enzymes and coenzymes (carbohydrates), HEK293 Cells, Gene Expression Regulation, Biocatalysis, biology.protein, lcsh:Q, Endothelium, Vascular |
| الوصف: | Apurinic/Apyrmidinic Endonuclease 1/Redox Factor-1 (APE1/Ref-1) is a reductant which is important for vascular homeostasis. SIRTUIN1 (SIRT1) is a lysine deacetylase that also promotes endothelium-dependent vasorelaxation. We asked if APE1/Ref-1 governs the redox state and activity of SIRT1, and whether SIRT1 mediates the effect of APE1/Ref-1 on endothelium-dependent vascular function. APE1/Ref-1 maintains sulfhydryl (thiol) groups of cysteine residues in SIRT1 in the reduced form and promotes endothelial SIRT1 activity. APE1/Ref-1 stimulates SIRT1 activity by targeting highly conserved vicinal thiols 371 and 374 which form a zinc tetra-thiolate motif in the deacetylase domain of SIRT1. Cysteine residues in the N-terminal redox domain of APE1/Ref-1 are essential for reducing SIRT1 and stimulating its activity. APE1/Ref-1 protects endothelial SIRT1 from hydrogen peroxide-induced oxidation of sulfhydryls and from inactivation. APE1/Ref-1 also promotes lysine deacetylation of the SIRT1 target endothelial nitric oxide synthase (eNOS). SIRT1 mutated at cysteines 371 and 374, which renders it non-reducible by APE1/Ref-1, prevents lysine deacetylation of eNOS by APE1/Ref-1. SIRT1 free thiol (reduced sulfhydryl) content and deacetylase activity are diminished in all examined tissues of APE1/Ref-1(+/-) mice, including the vasculature. Overexpression of SIRT1 in aortas of APE1/Ref-1(+/-) mice restores endothelium-dependent vasorelaxation and bioavailable nitric oxide (NO) to levels similar to those observed in wild-type mice. Thus, APE1/Ref-1, by maintaining functionally important cysteine sulfhydryls in SIRT1 in the reduced form, promotes endothelial SIRT1 activity. This reductive activation of endothelial SIRT1 by APE1/Ref-1 mediates the effect of APE1/Ref-1 on eNOS acetylation, promoting endothelium-derived NO and endothelium-dependent vasorelaxation. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4f555fee4d43a5950b3f2d27092e2c9fTest https://doi.org/10.1371/journal.pone.0065415Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4f555fee4d43a5950b3f2d27092e2c9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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