Biomedicine

NO Mechanism

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Science  22 Nov 2013:
Vol. 342, Issue 6161, pp. 910
DOI: 10.1126/science.342.6161.910-a
CREDIT: Z. HUANG ET AL., SCIENCE SIGNALING 6, 299 (29 OCTOBER 2013)

Although nitrogen-containing compounds have been used to treat heart failure for well over 1000 years, in many cases their mechanisms of action are unclear. Huang et al. now show that agents that increase the production of nitric oxide (NO) can influence heart function through S-nitrosylation of the enzyme GRK2; this protein kinase phosphorylates G protein—coupled receptors, most notably the β-adrenergic receptor, that have critical roles in regulating heart function. They found that GRK2 associates with endothelial NO synthase, the enzyme that produces NO, and nitrosylation of GRK2 inhibits its activity. In a mouse model of heart failure, treatment with agents that increased NO concentrations protected myocytes from cell death, but this effect was lost in animals expressing a mutant form of GRK2 that could not be S-nitrosylated.

Sci. Signal. 6, ra95 (2013).

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