title: Exogenous Hydrogen Sulﬁde Postconditioning Protects Isolated Rat Hearts From Ischemia/Reperfusion Injury Through Sirt1/PGC-1α Signaling Pathway.
abstract: Sirt1 is a highly conserved nicotinamide adenine dinucleotide (NAD(+)) dependent histone deacetylase which plays an important role in heart diseases. Studies performed with Sirt1 activators indicated that it protects cells from ischemia/ reperfusion (I/R) injury. The protective effects of H2S against I/R injury also have been recognized. Hence, the present study was designed to explore whether Sirt1/PGC-1α participates in the protection of exogenous H2S postconditioning against I/R injury in isolated rat hearts. Isolated rat hearts were subjected to 30 minutes of global ischemia followed by 60 minutes of reperfusion after 20 minutes of equilibrium. During this procedure, the hearts were exposed to NaHS (10 μmol/L) treatment in the absence or presence of the selective Sirt1 inhibitor EX-527 (10 μmol/L). NaHS exerted a protective effect on isolated rat hearts subjected to I/R, as shown by the improved expression of Sirt1/PGC-1α associated with restoration of Sirt1 nuclear localization, cardiac function, decreased myocardial infarct size, decreased myocardial enzyme release, and several biochemical parameters, including up-regulation of the ATP and SOD levels, and down-regulation of the MDA level. However, treatment with EX-527 could partially prevent the above effects of NaHS postconditioning. These results indicate that H2S confers protective effects against I/R injury through the activation of Sirt1/PGC1α.
authors.affiliation: Wuxi Medical School, Jiangnan University.
authors.forename: Ming-Zhu
authors.initials: MZ
authors.lastname: Hu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.forename: Hong-Ya
authors.initials: HY
authors.lastname: Mao
authors.forename: Qiong
authors.initials: Q
authors.lastname: Sheng
authors.forename: Bin
authors.initials: B
authors.lastname: Du
authors.forename: Jun-Liang
authors.initials: JL
authors.lastname: Chen
authors.forename: Qing-Feng
authors.initials: QF
authors.lastname: Pang
authors.forename: Yong
authors.initials: Y
authors.lastname: Ji
mesh_terms: D000255:Adenosine Triphosphate; D000818:Animals; D002227:Carbazoles; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D056564:Sirtuin 1 / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: C550547:6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide; D002227:Carbazoles; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D000255:Adenosine Triphosphate; C000606292:Sod1 protein, rat; D000072105:Superoxide Dismutase-1; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D006862:Hydrogen Sulfide