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Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4.

Publication ,  Journal Article
Sun, Q-A; Hess, DT; Nogueira, L; Yong, S; Bowles, DE; Eu, J; Laurita, KR; Meissner, G; Stamler, JS
Published in: Proc Natl Acad Sci U S A
September 20, 2011

Physiological sensing of O(2) tension (partial O(2) pressure, pO(2)) plays an important role in some mammalian cellular systems, but striated muscle generally is not considered to be among them. Here we describe a molecular mechanism in skeletal muscle that acutely couples changes in pO(2) to altered calcium release through the ryanodine receptor-Ca(2+)-release channel (RyR1). Reactive oxygen species are generated in proportion to pO(2) by NADPH oxidase 4 (Nox4) in the sarcoplasmic reticulum, and the consequent oxidation of a small set of RyR1 cysteine thiols results in increased RyR1 activity and Ca(2+) release in isolated sarcoplasmic reticulum and in cultured myofibers and enhanced contractility of intact muscle. Thus, Nox4 is an O(2) sensor in skeletal muscle, and O(2)-coupled hydrogen peroxide production by Nox4 governs the redox state of regulatory RyR1 thiols and thereby governs muscle performance. These findings reveal a molecular mechanism for O(2)-based signaling by an NADPH oxidase and demonstrate a physiological role for oxidative modification of RyR1.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 20, 2011

Volume

108

Issue

38

Start / End Page

16098 / 16103

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Sarcoplasmic Reticulum
  • Ryanodine Receptor Calcium Release Channel
  • Reverse Transcriptase Polymerase Chain Reaction
  • Reactive Oxygen Species
  • Rats
  • Rabbits
  • RNA Interference
  • Oxygen
  • Oxidation-Reduction
 

Citation

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Sun, Q.-A., Hess, D. T., Nogueira, L., Yong, S., Bowles, D. E., Eu, J., … Stamler, J. S. (2011). Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4. Proc Natl Acad Sci U S A, 108(38), 16098–16103. https://doi.org/10.1073/pnas.1109546108
Sun, Qi-An, Douglas T. Hess, Leonardo Nogueira, Sandro Yong, Dawn E. Bowles, Jerry Eu, Kenneth R. Laurita, Gerhard Meissner, and Jonathan S. Stamler. “Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4.Proc Natl Acad Sci U S A 108, no. 38 (September 20, 2011): 16098–103. https://doi.org/10.1073/pnas.1109546108.
Sun Q-A, Hess DT, Nogueira L, Yong S, Bowles DE, Eu J, et al. Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16098–103.
Sun, Qi-An, et al. “Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4.Proc Natl Acad Sci U S A, vol. 108, no. 38, Sept. 2011, pp. 16098–103. Pubmed, doi:10.1073/pnas.1109546108.
Sun Q-A, Hess DT, Nogueira L, Yong S, Bowles DE, Eu J, Laurita KR, Meissner G, Stamler JS. Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+ release channel by NADPH oxidase 4. Proc Natl Acad Sci U S A. 2011 Sep 20;108(38):16098–16103.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

September 20, 2011

Volume

108

Issue

38

Start / End Page

16098 / 16103

Location

United States

Related Subject Headings

  • Sulfhydryl Compounds
  • Sarcoplasmic Reticulum
  • Ryanodine Receptor Calcium Release Channel
  • Reverse Transcriptase Polymerase Chain Reaction
  • Reactive Oxygen Species
  • Rats
  • Rabbits
  • RNA Interference
  • Oxygen
  • Oxidation-Reduction