Role of Hydrogen Sulfide in the Cardioprotection Caused by Ischemic Preconditioning in the Rat Heart and Cardiac Myocytes

Abstract

Endogenous H(2)S is synthesized mainly by cystathionine gamma-lyase in the heart. The present study investigated the role of H(2)S in cardioprotection induced by ischemic preconditioning. We have examined the effect of endogenous H(2)S and exogenous application of NaHS (H(2)S donor) on cardiac rhythm in the isolated rat heart subjected to low-flow ischemia insults as well as cell viability and function in isolated myocytes exposed to simulated ischemia solution. Preconditioning with NaHS (SP) or ischemia (IP) for three cycles (3 min each cycle separated by 5 min of recovery) significantly decreased the duration and severity of ischemia/reperfusion-induced arrhythmias in the isolated heart while increasing cell viability and the amplitude of electrically induced calcium transients after ischemia/reperfusion in cardiac myocytes. Both IP and SP also significantly attenuated the decreased H(2)S production during ischemia. Moreover, decreasing endogenous H(2)S production significantly attenuated the protective effect of IP in both the isolated heart and isolated cardiac myocytes. Blockade of protein kinase C with chelerythrine or bisindolylmaleimide I as well as ATP-sensitive K(+) (K(ATP)) channel with glibenclamide (a nonselective K(ATP) blocker) and HMR-1098 (1-[[5-[2-(5-Chloro-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea) (a sarcolemmal K(ATP) channel blocker) reversed the cardioprotection induced by SP or IP. However, blockade of mitochondrial K(ATP) channels with 5-hydroxydecanoic acid had no effect on the cardioprotection of SP, suggesting that, unlike the mechanism involved in IP, mitochondrial K(ATP) channels most probably do not play a major role in the cardioprotection of SP. Our findings suggest that endogenous H(2)S contributes to cardioprotection induced by IP, which effect may involve protein kinase C and sarcolemmal K(ATP) channels.

Hydrogen Sulfide Inhibits High Glucose-induced Matrix Protein Synthesis by Activating AMP-activated Protein Kinase in Renal Epithelial Cells

“…These protective phenotypes were reproduced by myocardium-specific overexpression of cystathionine ␥-lyase (5). Other mechanisms contributing to hydrogen sulfide protection of myocardium include opening of the K-ATP channels in mitochondria and/or sarcolemma (63,64), induction of antioxidant genes by Nrf-2, and resistance to apoptosis by stimulation of survival pathways (65). Recruitment of specific pathways by hydrogen sulfide in diverse tissues is likely to be dependent on the context of injury.…”

Nitrative thioredoxin inactivation as a cause of enhanced myocardial ischemia/reperfusion injury in the aging heart

“…Recent in vitro studies demonstrate that Trx interacts directly with, and inhibits, the activity of apoptosis-regulating kinase-1 (ASK1), a mitogen-activated protein (MAP) kinase that activates two pro-apoptotic kinases, p38 MAP kinase (MAPK) and c-Jun N-terminal kinase (JNK) [7]. In aged mouse livers, the ratio of ASK1/Trx-ASK1 (free ASK1/Trx-binding ASK1) increases and this correlates with the increased basal activity of the p38 MAPK pathway [8]. These results suggest that Trx may play a critical role in cell proliferation and cell death in aging.…”

Novel insights into the role of HSP90 in cytoprotection of H2S against chemical hypoxia-induced injury in H9c2 cardiac myocytes

“…H 2 S has been reported to reduce cardiomyocyte apoptosis in vitro and in vivo after myocardial ischemic-reperfusion (18,19). Inhibition of endogenous H 2 S production by H 2 S synthesis inhibitors obviously attenuated the protective effect of ischemic pre-conditioning in both the isolated heart and isolated cardiac myocytes (26). Our more recent study indicated that H 2 S protects H9c2 cells against cocl 2 -induced cytotoxicity and apoptosis by its antioxidant effect (22).…”

“…H 2 S protects astrocytes and neurons against oxidative insult (12,13). Our previous study also showed that H 2 S possessed antioxidant and anti-apoptotic effects against injury induced by the Aβ [25][26][27][28][29][30][31][32][33][34][35] peptide in PC12 cells (14). Similarly, in numerous cell and animal models of heart diseases, it has been demonstrated that the mechanisms of H 2 S cytoprotection underlie the inhibition of myocardial inflammation and preservation of both mitochondrial structure and function (15)(16)(17)(18)(19).…”