Skeletal muscle sarcoplasmic reticulum contains a NADH-dependent oxidase that generates superoxide

Ruohong Xia, Jason A. Webb, Lisa L.M. Gnall, Kerry Cutler, Jonathan J. Abramson

Research output: Contribution to journalArticlepeer-review

99 Scopus citations

Abstract

Skeletal muscle sarcoplasmic reticulum (SR) is shown to contain an NADH-dependent oxidase (NOX) that reduces molecular oxygen to generate superoxide. Its activity is coupled to an activation of the Ca2+ release mechanism, as evident by stimulation in the rate of high-affinity ryanodine binding. NOX activity, coupled to the production of superoxide, is not derived from the mitochondria but is SR in origin. The SR preparation also contains a significant NADH oxidase activity, which is not coupled to the production of superoxide and appears to be mitochondrial in origin. This mitochondrial component is preferentially associated with the terminal cisternae region of the SR. Its activity is inhibited by diphenylene iodonium (10 μM), antimycin A (200 nM), and rotenone (40 nM) but is not coupled to the generation of superoxide or the stimulation of the ryanodine receptor. The rate of superoxide production per milligram of protein is larger in SR than in mitochondria. This NOX may be a major source of oxidative stress in muscle.

Original languageEnglish (US)
Pages (from-to)C215-C221
JournalAmerican Journal of Physiology - Cell Physiology
Volume285
Issue number1 54-1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

Keywords

  • NADH-dependent superoxide production
  • Oxidative stress
  • Ryanodine receptor
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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