The subcellular localization of neuronal nitric oxide synthase determines the downstream effects of NO on myocardial function

AimsIn healthy hearts, the neuronal nitric oxide synthase (nNOS) is predominantly localized to the sarcoplasmic reticulum (SR), where it regulates the ryanodine receptor Ca2+ release channel (RyR2) and phospholamban (PLB) phosphorylation, and to a lesser extent to the sarcolemmal membrane where it inhibits the L-type Ca2+ current (ICa). However, in failing hearts, impaired relaxation and depressed inotropy are associated with a larger proportion of nNOS being localized to the sarcolemmal membrane. Whether there is a causal relationship between altered myocardial function and subcellular localization of nNOS remains to be assessed.Methods and resultsAdenoviruses (AdV) encoding for a human nNOS.eGFP fusion protein or eGFP were injected into the left ventricle (LV) of nNOS−/− mice. nNOS.eGFP localized to the sarcolemmal and t-tubular membrane and immunoprecipitated with syntrophin and caveolin-3 but not with RyR2. Myocardial transduction of nNOS.eGFP resulted in a significantly increased NOS activity (10-fold, P
Source: Cardiovascular Research - Category: Cardiology Source Type: research

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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
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Source: J Cell Mol Med - Category: Molecular Biology Authors: Tags: J Cell Mol Med Source Type: research
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Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research
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Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
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Bioconjugate ChemistryDOI: 10.1021/acs.bioconjchem.9b00291
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