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.
Phospholamban Thiols Play a Central Role in Activation of the Cardiac Muscle Sarcoplasmic Reticulum Calcium Pump by Nitroxyl / Froehlich Jeffrey, P.; Mahaney James, E.; Keceli, Gizem; Pavlos Christopher, M.; Goldstein, Russell; Redwood Abiona, J.; Sumbilla, Carlota; Lee Dong, I.; Tocchetti, CARLO GABRIELE; Kass David, A.; Paolocci, Nazareno; Toscano John, P.. - In: BIOCHEMISTRY. - ISSN 0006-2960. - 47:50(2008), pp. 13150-13152. [10.1021/bi801925p]
Phospholamban Thiols Play a Central Role in Activation of the Cardiac Muscle Sarcoplasmic Reticulum Calcium Pump by Nitroxyl
TOCCHETTI, CARLO GABRIELE;
2008
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.File | Dimensione | Formato | |
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