Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl

Jeffrey P. Froehlich, James E. Mahaney, Gizem Keceli, Christopher M. Pavlos, Russell Goldstein, Abiona J. Redwood, Carlota Sumbilla, Dong Lee, Carlo G. Tocchetti, David A Kass, Nazareno Paolocci, John P. Toscano

Research output: Contribution to journalArticle

Abstract

Nitroxyl (HNO) donated by Angeli's salt activates uptake of Ca2+ by the cardiac SR Ca2+ 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 Ca2+ pump.

Original languageEnglish (US)
Pages (from-to)13150-13152
Number of pages3
JournalBiochemistry®
Volume47
Issue number50
DOIs
StatePublished - Dec 16 2008

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Sarcoplasmic Reticulum
Sulfhydryl Compounds
Muscle
Myocardium
Chemical activation
Pumps
Calcium
Microsomes
Disulfides
Insects
Conformations
nitroxyl
phospholamban
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Froehlich, J. P., Mahaney, J. E., Keceli, G., Pavlos, C. M., Goldstein, R., Redwood, A. J., ... Toscano, J. P. (2008). Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl. Biochemistry®, 47(50), 13150-13152. https://doi.org/10.1021/bi801925p

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; Tocchetti, Carlo G.; Kass, David A; Paolocci, Nazareno; Toscano, John P.

In: Biochemistry®, Vol. 47, No. 50, 16.12.2008, p. 13150-13152.

Research output: Contribution to journalArticle

Froehlich, JP, Mahaney, JE, Keceli, G, Pavlos, CM, Goldstein, R, Redwood, AJ, Sumbilla, C, Lee, D, Tocchetti, CG, Kass, DA, Paolocci, N & Toscano, JP 2008, 'Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl', Biochemistry®, vol. 47, no. 50, pp. 13150-13152. https://doi.org/10.1021/bi801925p
Froehlich JP, Mahaney JE, Keceli G, Pavlos CM, Goldstein R, Redwood AJ et al. Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl. Biochemistry®. 2008 Dec 16;47(50):13150-13152. https://doi.org/10.1021/bi801925p
Froehlich, Jeffrey P. ; Mahaney, James E. ; Keceli, Gizem ; Pavlos, Christopher M. ; Goldstein, Russell ; Redwood, Abiona J. ; Sumbilla, Carlota ; Lee, Dong ; Tocchetti, Carlo G. ; Kass, David A ; Paolocci, Nazareno ; Toscano, John P. / Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl. In: Biochemistry®. 2008 ; Vol. 47, No. 50. pp. 13150-13152.
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