Search

The present study aimed to investigate the role of hydrogen sulphide ([H.sub.2]S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous [H.sub.2]S production with D-L-propargylglycine. Moreover, IPostC significantly stimulated [H.sub.2]S synthesis enzyme activity during the early period of reperfusion. However, D-L-propargylglycine only attenuated the IPostC-induced activation of PKC-[alpha] and PKC-[epsilon] but not that of PKC-[delta], Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous [H.sub.2]S contributes partially to the cardioprotection of IPostC via stimulating PKC-[alpha] and PKC-[epsilon]. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous NaHS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 [micro]M) or PKC with chelerythrine (10 [micro]M) abolished the cardioprotection induced by [H.sub.2]S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous [H.sub.2]S contributes to IPostC-induced cardioprotection. [H.sub.2]S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways. Akt; protein kinase C; hydrogen sulphide; endothelial nitric oxide synthase

The present study was aimed to investigate the regulatory effect of protein kinase C (PKC) on intracellular [Ca.sup.2+] handling in hydrogen sulfide ([H.sub.2]S)-preconditioned cardiomyocytes and its consequent effects on iscbemia challenge. Immunoblot analysis was used to assess PKC isoform translocation in the rat cardiomyocytes 20 h after NaHS (an [H.sub.2]S donor, [10.sup.-4] M) preconditioning (SP, 30 min). Intracellular [Ca.sup.2+] was measured with a spectrofluorometric method using fura-2 ratio as an indicator. Cell length was compared before and after ischemia-reperfusion insults to indicate the extent of hypercontracture. SP motivated translocation of PKC[alpha], PKC[epsilon], and PKC[delta] to membrane fraction but only translocation of PKC[epsilon] and PKC[delta] was abolished by an ATP-sensitive potassium channel blocker glibenclamide. It was also found that SP significantly accelerated the decay of both electrically and caffeine-induced intracellular [[Ca.sup.2+]] transients, which were reversed by a selective PKC inhibitor cbelerythrine. These data suggest that SP facilitated [Ca.sup.2+] removal via both accelerating uptake of [Ca.sup.2+] into sarcoplasmic reticulum and enhancing [Ca.sup.2+] extrusion through [Na.sup.+]/[Ca.sup.2+] exchanger in a PKC-dependent manner. Furthermore, blockade of PKC also attenuated the protective effects of SP against [Ca.sup.2+] overload during ischemia and against myocyte hypercontracture at the onset of reperfusion. We demonstrate for the first time that SP activates PKC[alpha], PKC[epsilon], and PKC[delta] in cardiomyocytes via different signaling mechanisms. Such PKC activation, in turn, protects the heart against ischemia-reperfusion insults at least partly by ameliorating intracellular [Ca.sup.2+] handling. protein kinase C isoforms; ischemia and reperfusion; cardioprotection; ATP-sensitive potassium channel

The present study aimed to investigate the role of hydrogen sulphide (H2S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous H2S production with D-L-propargylglycine. Moreover, IPostC significantly stimulated H2S synthesis enzyme activity during the early period of reperfusion. However, D-L-propargylglycine only attenuated the IPostC-induced activation of PKC-α and PKC-ε but not that of PKC-δ, Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous H2S contributes partially to the cardioprotection of IPostC via stimulating PKC-α and PKC-ε. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous Na}IS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 nM) or PKC with chelerythrine (10 µM) abolished the cardioprotection induced by H2S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous H2S contributes to IPostC-induced cardioprotection. H2S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways. [ABSTRACT FROM AUTHOR]

The present study was aimed to investigate the regulatory effect of protein kinase C (PKC) on intracellular Ca2+ handling in hydrogen sulfide (H2S)-preconditioned cardiomyocytes and its consequent effects on ischemia challenge. Immunoblot analysis was used to assess PKC isoform translocation in the rat cardiomyocytes 20 h after NaHS (an H2S donor, 10-4 M) preconditioning (SP, 30 mm). Intracellular Ca2+ was measured with a spectrofluorometric method using fura-2 ratio as an indicator. Cell length was compared before and after ischemia-reperfusion insults to indicate the extent of hypercontracture. SP motivated translocation of PKCα, PKCϵ, and PKCδ to membrane fraction but only translocation of PKCϵ and PKCδ was abolished by an ATP-sensitive potassium channel blocker glibenclamide. It was also found that SP significantly accelerated the decay of both electrically and caffeine- induced intracellular [Ca2+] transients, which were reversed by a selective PKC inhibitor chelerythrine. These data suggest that SP facilitated Ca2+ removal via both accelerating uptake of Ca2+ into sarcoplasmic reticulum and enhancing Ca2+ extrusion through Na+/Ca2+ exchanger in a PKC-dependent manner. Furthermore, blockade of PKC also attenuated the protective effects of SP against Ca2+ overload during ischemia and against myocyte hypercontracture at the onset of reperfusion. We demonstrate for the first time that SP activates PKCα, PKCϵ, and PKCδ in cardiomyocytes via different signaling mechanisms. Such PKC activation, in turn, protects the heart against ischemia-reperfusion insults at least partly by ameliorating intracellular Ca2+ handling. [ABSTRACT FROM AUTHOR]