Abstract
Nitroxyl (HNO) donated by Angeli's salt activates uptake of Ca(2+) by the cardiac SR Ca(2+) pump (SERCA2a). To determine whether HNO achieves this by a direct interaction with SERCA2a or its regulatory protein, phospholamban (PLN), we measured its effects on SERCA2a activation (as reflected in dephosphorylation) using insect cell microsomes expressing SERCA2a with or without PLN (wild-type and Cys --> Ala mutant). The results show that activation of SERCA2a dephosphorylation by HNO is PLN-dependent and that PLN thiols are targets for HNO. We conclude that HNO produces a disulfide bond that alters the conformation of PLN, relieving inhibition of the Ca(2+) pump.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antioxidants / chemistry
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Antioxidants / metabolism
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Calcium-Binding Proteins / chemistry
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Calcium-Binding Proteins / physiology*
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Dogs
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Enzyme Activation / physiology
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Free Radicals / chemistry
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Free Radicals / metabolism
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Insecta
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Microsomes / enzymology
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Myocardium / enzymology*
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Nitrogen Oxides / chemistry*
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Nitrogen Oxides / metabolism
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Phosphorylation
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Sarcoplasmic Reticulum / enzymology*
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Sarcoplasmic Reticulum Calcium-Transporting ATPases / antagonists & inhibitors
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Sarcoplasmic Reticulum Calcium-Transporting ATPases / chemistry
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Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*
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Sulfhydryl Compounds / chemistry
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Sulfhydryl Compounds / physiology*
Substances
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Antioxidants
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Calcium-Binding Proteins
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Free Radicals
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Nitrogen Oxides
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Sulfhydryl Compounds
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phospholamban
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Sarcoplasmic Reticulum Calcium-Transporting ATPases
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nitroxyl