Journal
CIRCULATION RESEARCH
Volume 104, Issue 6, Pages 720-U35Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.108.188441
Keywords
sarcoplasmic reticulum ATPase; SERCA; nitroxyl; glutathiolation; cardiac myocytes
Funding
- NIH [HL-061639, HL-064750, HL31607]
- Boston University Cardiovascular Proteomics Center [N01-HV-28178]
- La Fondation pour la Recherche Medicale [SPE20051105207]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available