Hydrogen sulfide (H2S) nitric oxide (NO) and carbogen monoxide (CO) have recently been described as endogenous gasotransmitters. Akin NO and CO, H2S plays a role in cellular signaling. We demonstrated that NO and its sibling species HNO can exert preconditioning-like effects in models of ischemia/reperfusion. H2S is constitutively produced by two different enzymes: cystathionin-β-sinthase and cystathionine-γ-lyase with a prevalence in the nervous system and in the cardiovascular system respectively. Although the mechanism of action of H2S has not yet been elucidated, the vasorelaxant effect is mimicked by KATP channel opener and blocked by KATP channels inhibitor (Glibenclamide). Glibenclamide can also partially reduce the negative inotropic effect of H2S in in vivo rat hearts. As we previously showed in an isolated heart model, the cardioprotective effects of NO and HNO can be blocked by mitochondrial KATP channels inhibitors. Evidences have emerged about the cytoprotective effect of H2S in ischemia/reperfusion models and some authors suggest a positive feedback action on NO production through the upregulation of the inducible form of NO sinthase. While H2S cytotoxicity is proved to be mediated by reactive oxygen species formation and mitochondrial depolarization no evidences have so far emerged about the involvement of mitochondria in the prosurvival effect of H2S. We showed that H2S can modulate prosurvival activity of kinases such as ERK, Akt and GSK. It is likely that intracellular concentration of H2S is finely regulated and that its action is bi-modal with deleterious effects for high concentrations and with functional signaling properties at micromolar concentrations.
INVOLVEMENT OF MITOCHONDRIA IN THE PROTECTIVE EFFECT OF HYDROGEN SULFIDE AGAINST OXIDATIVE STRESS IN CARDIOMYOCYTES
MANCARDI, Daniele;PAGLIARO, Pasquale;PENNA, Claudia
2008-01-01
Abstract
Hydrogen sulfide (H2S) nitric oxide (NO) and carbogen monoxide (CO) have recently been described as endogenous gasotransmitters. Akin NO and CO, H2S plays a role in cellular signaling. We demonstrated that NO and its sibling species HNO can exert preconditioning-like effects in models of ischemia/reperfusion. H2S is constitutively produced by two different enzymes: cystathionin-β-sinthase and cystathionine-γ-lyase with a prevalence in the nervous system and in the cardiovascular system respectively. Although the mechanism of action of H2S has not yet been elucidated, the vasorelaxant effect is mimicked by KATP channel opener and blocked by KATP channels inhibitor (Glibenclamide). Glibenclamide can also partially reduce the negative inotropic effect of H2S in in vivo rat hearts. As we previously showed in an isolated heart model, the cardioprotective effects of NO and HNO can be blocked by mitochondrial KATP channels inhibitors. Evidences have emerged about the cytoprotective effect of H2S in ischemia/reperfusion models and some authors suggest a positive feedback action on NO production through the upregulation of the inducible form of NO sinthase. While H2S cytotoxicity is proved to be mediated by reactive oxygen species formation and mitochondrial depolarization no evidences have so far emerged about the involvement of mitochondria in the prosurvival effect of H2S. We showed that H2S can modulate prosurvival activity of kinases such as ERK, Akt and GSK. It is likely that intracellular concentration of H2S is finely regulated and that its action is bi-modal with deleterious effects for high concentrations and with functional signaling properties at micromolar concentrations.
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