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

doi:10.1021/bi801925p

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

76 Scopus citations

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 language	English (US)
Pages (from-to)	13150-13152
Number of pages	3
Journal	Biochemistry
Volume	47
Issue number	50
DOIs	https://doi.org/10.1021/bi801925p
State	Published - Dec 16 2008

ASJC Scopus subject areas

Biochemistry

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Froehlich, J. P., Mahaney, J. E., Keceli, G., Pavlos, C. M., Goldstein, R., Redwood, A. J., Sumbilla, C., Lee, D. I., Tocchetti, C. G., Kass, D. A., Paolocci, N., & 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

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

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.",

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

year = "2008",

month = dec,

day = "16",

doi = "10.1021/bi801925p",

language = "English (US)",

volume = "47",

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journal = "Biochemistry",

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TY - JOUR

T1 - Phospholamban thiols play a central role in activation of the cardiac muscle sarcoplasmic reticulum calcium pump by nitroxyl

AU - Froehlich, Jeffrey P.

AU - Mahaney, James E.

AU - Keceli, Gizem

AU - Pavlos, Christopher M.

AU - Goldstein, Russell

AU - Redwood, Abiona J.

AU - Sumbilla, Carlota

AU - Lee, Dong I.

AU - Tocchetti, Carlo G.

AU - Kass, David A.

AU - Paolocci, Nazareno

AU - Toscano, John P.

PY - 2008/12/16

Y1 - 2008/12/16

N2 - 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.

AB - 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.

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U2 - 10.1021/bi801925p

DO - 10.1021/bi801925p

M3 - Article

C2 - 19053265

AN - SCOPUS:57649128299

SN - 0006-2960

VL - 47

SP - 13150

EP - 13152

JO - Biochemistry

JF - Biochemistry

IS - 50

ER -

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

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