Nitroxyl (HNO) increases the maximal activation of SERCA in adult rat ventricular myocytes via S-glutathiolation at cysteine 674.
Nitroxyl exerts its inotropic and lusitropic effects in the myocardium by activating SERCA through S-glutathiolation at cysteine 674.
Nitroxyl (HNO) exerts inotropic and lusitropic effects in myocardium, in part via activation of SERCA (sarcoplasmic reticulum calcium ATPase). To elucidate the molecular mechanism, adult rat ventricular myocytes were exposed to HNO derived from Angeli's salt. HNO increased the maximal rate of thapsigargin-sensitive Ca2+ uptake mediated by SERCA in sarcoplasmic vesicles and caused reversible oxidative modification of SERCA thiols. HNO increased the S-glutathiolation of SERCA, and adenoviral overexpression of glutaredoxin-1 prevented both the HNO-stimulated oxidative modification of SERCA and its activation, as did overexpression of a mutated SERCA in which cysteine 674 was replaced with serine. Thus, HNO increases the maximal activation of SERCA via S-glutathiolation at cysteine 674.
Lancel et al. (Fri,) reported a other. Nitroxyl (HNO) derived from Angeli's salt was evaluated on Maximal rate of thapsigargin-sensitive Ca2+ uptake mediated by SERCA and S-glutathiolation of SERCA. Nitroxyl (HNO) increases the maximal activation of SERCA in adult rat ventricular myocytes via S-glutathiolation at cysteine 674.
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