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Title: Hydrogen sulfide produces cardioprotective effects against ischemia/reperfusion injury via regulation of intracelluar PH
Authors: LI YU
Keywords: hydrogen sulfide, intracelluar pH, ischemia/reperfusion, Na+ /H+ exchanger, Cl- /HCO3- exchanger, cardioprotection
Issue Date: 11-Jul-2012
Source: LI YU (2012-07-11). Hydrogen sulfide produces cardioprotective effects against ischemia/reperfusion injury via regulation of intracelluar PH. ScholarBank@NUS Repository.
Abstract: Intracellular pH(pHi) is an important endogenous modulator of cardiac function. Hydrogen sulfide(H2S) has been reported to produce cardioprotection. My study was designed to investigate the pH regulatory effect of H2S in rat cardiac myocytes and evaluate its contribution to cardioprotection. It was found that sodium hydrosulfide(NaHS) produced sustained decreases in pHi in the rat myocytes. NaHS also abolished the intracellular alkalinization caused by trans-(?)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methane-sulfonate hydrate(U50,488H), which activates NHEs. Moreover, NaHS was found to significantly suppress NHE-1 activity. Both NaHS and cariporide or [5-(2-methyl-5-fluorophenyl)furan-2-ylcarbonyl]guanidine(KR-32568) protected the cardiomyocytes against ischemia/reperfusion. Functional study showed that perfusion with NaHS significantly improved post-ischemic contractile function in isolated rat hearts. Blockade of phosphoinositide 3-kinase(PI3K) with 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one(LY294002), Akt with Akt VIII, or protein kinase G(PKG) with (9S,10R,12R)-2,3,9,10,11,12-hexahydro-10- methoxy-2,9-dimethyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg: 3?,2?,1?-kl]pyrrolo[3,4-i][1,6]]enzodiazocine-10-carboxylic acid, methyl ester(KT5823) significantly attenuated NaHS-induced cardioprotection. In conclusion, these results demonstrated that H2S produced cardioprotection via the suppression of NHE-1 activity involving a PI3K/Akt/PKG-dependent mechanism.
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