Sci. Signal., 29 October 2013
NO More Heart DamageDamage caused by the lack of oxygen and nutrients that occurs during myocardial ischemia can result in heart failure. A therapeutic strategy that helps to limit the effects of heart failure is to increase signaling through G protein–coupled receptors (GPCRs) by inhibiting GRK2 (GPCR kinase 2), a kinase that desensitizes GPCRs. Another therapeutic strategy provides S-nitrosothiols, such as nitric oxide, which can be added to proteins in a posttranslational modification called S-nitrosylation. Huang et al. found that the ability of S-nitrosothiols to enhance cardiomyocyte survival after ischemic injury required the S-nitrosylation of GRK2, a modification that inhibits this kinase. Mice bearing a form of GRK2 that could not be S-nitrosylated were more susceptible to cardiac damage after ischemia. These results suggest that therapeutic strategies that promote the S-nitrosylation of GRK2 could be used to treat heart failure after myocardial ischemia.
Citation: Z. M. Huang, E. Gao, F. V. Fonseca, H. Hayashi, X. Shang, N. E. Hoffman, J. K. Chuprun, X. Tian, D. G. Tilley, M. Madesh, D. J. Lefer, J. S. Stamler, W. J. Koch, Convergence of G Protein–Coupled Receptor and S-Nitrosylation Signaling Determines the Outcome to Cardiac Ischemic Injury. Sci. Signal. 6, ra95 (2013).
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