Nitroxyl activates SERCA in cardiac myocytes via glutathiolation of cysteine 674.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 19265039.
- Also identified by DOI 10.1161/CIRCRESAHA.108.188441 and PMC identifier 3046805.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
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.
Medical subject headings
- Antioxidants
- Glutathione
- Myocardium
- Myocytes, Cardiac
- Nitrogen Oxides
- Protein Processing, Post-Translational
- Sarcoplasmic Reticulum Calcium-Transporting ATPases