Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.redox.2020.101813
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dc.titlePolysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-kappa B and STAT3
dc.contributor.authorSun, Hai-Jian
dc.contributor.authorXiong, Si-Ping
dc.contributor.authorCao, Xu
dc.contributor.authorCao, Lei
dc.contributor.authorZhu, Meng-Yuan
dc.contributor.authorWu, Zhi-Yuan
dc.contributor.authorBian, Jin-Song
dc.date.accessioned2022-04-19T02:11:35Z
dc.date.available2022-04-19T02:11:35Z
dc.date.issued2021-01-01
dc.identifier.citationSun, Hai-Jian, Xiong, Si-Ping, Cao, Xu, Cao, Lei, Zhu, Meng-Yuan, Wu, Zhi-Yuan, Bian, Jin-Song (2021-01-01). Polysulfide-mediated sulfhydration of SIRT1 prevents diabetic nephropathy by suppressing phosphorylation and acetylation of p65 NF-kappa B and STAT3. REDOX BIOLOGY 38. ScholarBank@NUS Repository. https://doi.org/10.1016/j.redox.2020.101813
dc.identifier.issn22132317
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/219267
dc.description.abstractDiabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.
dc.language.isoen
dc.publisherELSEVIER
dc.sourceElements
dc.subjectScience & Technology
dc.subjectLife Sciences & Biomedicine
dc.subjectBiochemistry & Molecular Biology
dc.subjectDiabetic nephropathy
dc.subjectReactive oxygen species
dc.subjectPolysulfides
dc.subjectHydrogen sulfide
dc.subjectSIRT1
dc.subjectHYDROGEN-SULFIDE H2S
dc.subjectOXIDATIVE STRESS
dc.subjectRENAL FIBROSIS
dc.subjectKIDNEY-DISEASE
dc.subjectSULFANE SULFUR
dc.subjectNITRIC-OXIDE
dc.subjectINFLAMMATION
dc.subjectMETABOLISM
dc.subjectAPOPTOSIS
dc.subjectPATHWAY
dc.typeArticle
dc.date.updated2022-04-18T08:48:50Z
dc.contributor.departmentDEPT OF PHARMACOLOGY
dc.description.doi10.1016/j.redox.2020.101813
dc.description.sourcetitleREDOX BIOLOGY
dc.description.volume38
dc.published.statePublished
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