Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes

Pan, Tingting; Feng, Zhan-Ning; Lee, Shiau Wei; Moore, Philip K.; Bian, Jin-Song

doi:10.1016/j.yjmcc.2005.10.003

Cited by 186 publications

(167 citation statements)

References 40 publications

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“…nervous system (1). We proved that H 2 S exerted a wide range of biological functions, including neuroprotection (8,14), cardioprotection (20,21), antihypertension (13), and osteoblastic protection (37). Most of these functions are attributed to its antioxidant effects.…”

Section: Innovationmentioning

confidence: 84%

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

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116

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Aims: Mitochondrion is considered as the major source of intracellular reactive oxygen species (ROS). H 2 S has been reported to be an antioxidant, but its mechanism remains largely elusive. P66Shc is an upstream activator of mitochondrial redox signaling. The aim of this study was to explore whether the antioxidant effect of H 2 S is mediated by p66Shc. Results: Application of exogenous H 2 S with its donor, NaHS, or overexpression of its generating enzyme, cystathionine b-synthase, induced sulfhydration of p66Shc, but inhibited its phosphorylation caused by H 2 O 2 /D-galactose in SH-SY5Y cells or in the mice cortex. H 2 S also decreased mitochondrial ROS production and protected neuronal cells against stress-induced senescence. PKC bII and PP2A are the two key proteins to regulate p66Shc phosphorylation. Although H 2 S failed to affect the activities of these two proteins, it disrupted their association. Cysteine-59 resides in proximity to serine-36, the phosphorylation site of p66Shc. The C59S mutant attenuated the above-described biological function of H 2 S. Innovation: We revealed a novel mechanism for the antioxidant effect of H 2 S and its role in oxidative stress-related diseases. Conclusion: H 2 S inhibits mitochondrial ROS production via the sulfhydration of Cys-59 residue, which in turn, prevents the phosphorylation of p66Shc. Antioxid. Redox Signal. 21, 2531-2542.

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Section: Innovationmentioning

confidence: 84%

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Xie

Shi²,

Xie³

et al. 2014

Antioxidants & Redox Signaling

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116

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“…However, it has recently been shown that complex I inhibition may underlie the cardioprotective effects of agents such as amobarbital [29,30], volatile anesthetics [60], and ranolazine [61]. Complex II inhibitors such as diazoxide [60] and 3-nitropropionic acid [62,63] are also cardioprotective, as are complex IV inhibitors such as hydrogen sulfide [64,65] and carbon monoxide [66]. In addition it is reported that glycolysis is inhibited in IPC [67], and it is known that a key regulator of glycolysis, GAPDH, is a target for S-nitrosation [68].…”

Section: Discussionmentioning

confidence: 99%

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

Nadtochiy

Burwell

Brookes

2007

Journal of Molecular and Cellular Cardiology

132

118

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Mitochondrial dysfunction is a key pathologic event in cardiac ischemia-reperfusion (IR) injury, and protection of mitochondrial function is a potential mechanism underlying ischemic preconditioning (IPC). Acknowledging the role of nitric oxide (NO • ) in IPC, it was hypothesized that mitochondrial protein S-nitrosation may be a cardioprotective mechanism. The reagent S-nitroso-2-mercaptopropionyl-glycine (SNO-MPG) was therefore developed to enhance mitochondrial Snitrosation and elicit cardioprotection. Within cardiomyocytes, mitochondrial proteins were effectively S-nitrosated by SNO-MPG. Consistent with the recent discovery of mitochondrial complex I as an S-nitrosation target, SNO-MPG inhibited complex I activity and cardiomyocyte respiration. The latter effect was insensitive to the NO • scavenger c-PTIO, indicating no role for NO • -mediated complex IV inhibition. A cardioprotective role for reversible complex I inhibition has been proposed, and consistent with this SNO-MPG protected cardiomyocytes from simulated IR injury. Further supporting a cardioprotective role for endogenous mitochondrial S-nitrosothiols, patterns of protein S-nitrosation were similar in mitochondria isolated from Langendorff perfused hearts subjected to IPC, and mitochondria or cells treated with SNO-MPG. The functional recovery of perfused hearts from IR injury was also improved under conditions which stabilized endogenous S-nitrosothiols (i.e. dark), or by pre-ischemic administration of SNO-MPG. Mitochondria isolated from SNO-MPG-treated hearts at the end of ischemia exhibited improved Ca 2+ handling and lower ROS generation. Overall these data suggest that mitochondrial S-nitrosation and complex I inhibition constitute a protective signaling pathway that is amenable to pharmacologic augmentation.

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“…Moreover, researchers have found that preconditioning and postconditioning with H 2 S produced cardioprotective effects against ischemic injury via the regulation of protein kinase C, K ATP channels, cyclooxygenase-2, NO, p42/44-mitogen-activated protein kinase, phosphoinositol-3-kinase (PI3K)/Akt, and GSK3␤ pathways Yong et al, 2008a;Yao et al, 2010). More importantly, endogenous H 2 S was found to contribute to the cardioprotection induced by ischemic preconditioning and postconditioning Pan et al, 2006;Yong et al, 2008a). In addition, H 2 S may produce a proangiogenic effect (Cai et al, 2007) that can contribute to its cardioprotective action.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Sulfide Regulates Na⁺/H⁺ Exchanger Activity via Stimulation of Phosphoinositide 3-Kinase/Akt and Protein Kinase G Pathways

Liu²,

Neo³

et al. 2011

J Pharmacol Exp Ther

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Intracellular pH (pH i ) is an important endogenous modulator of cardiac function. Inhibition of Naϩ /H ϩ exchanger-1 (NHE-1) protects the heart by preventing Ca 2ϩ overload during ischemia/reperfusion. Hydrogen sulfide (H 2 S) has been reported to produce cardioprotection. The present study was designed to investigate the pH regulatory effect of H 2 S in rat cardiac myocytes and evaluate its contribution to cardioprotection. It was found that sodium hydrosulfide (NaHS), at a concentration range of 10 to 1000 M, produced sustained decreases in pH i in the rat myocytes in a concentration-dependent manner. NaHS also abolished the intracellular alkalinization caused by trans-(Ϯ) -3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methane-sulfonate hydrate (U50,488H), which activates NHEs. Moreover, when measured with an NHCl 4 prepulse method, 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), two NHE inhibitors, protected the myocytes against ischemia/reperfusion injury. However, coadministration of NaHS with KR-32568 did not produce any synergistic effect. Functional study showed that perfusion with NaHS significantly improved postischemic contractile function in isolated rat hearts subjected to ischemia/reperfusion. 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: 3Ј,2Ј,1Ј-kl]pyrrolo[3,4-i][1,6]]enzodiazocine-10-carboxylic acid, methyl ester (KT5823) significantly attenuated NaHS-suppressed NHE-1 activity and/or NaHS-induced cardioprotection. Although KT5823 failed to affect NaHS-induced Akt phosphorylation, Akt inhibitor did attenuate NaHS-stimulated PKG activity. In conclusion, this work demonstrated for the first time that H 2 S produced cardioprotection via the suppression of NHE-1 activity involving a PI3K/Akt/PKG-dependent mechanism.

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Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes

Cited by 186 publications

References 40 publications

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

Hydrogen Sulfide Regulates Na⁺/H⁺ Exchanger Activity via Stimulation of Phosphoinositide 3-Kinase/Akt and Protein Kinase G Pathways

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Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes

Cited by 186 publications

References 40 publications

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Sulfhydration of p66Shc at Cysteine59 Mediates the Antioxidant Effect of Hydrogen Sulfide

Cardioprotection and mitochondrial S-nitrosation: Effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia–reperfusion injury

Hydrogen Sulfide Regulates Na+/H+ Exchanger Activity via Stimulation of Phosphoinositide 3-Kinase/Akt and Protein Kinase G Pathways

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Hydrogen Sulfide Regulates Na⁺/H⁺ Exchanger Activity via Stimulation of Phosphoinositide 3-Kinase/Akt and Protein Kinase G Pathways