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


Journal Article

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 microM), 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.

Full Text

Duke Authors

Cited Authors

  • Xia, R; Webb, JA; Gnall, LLM; Cutler, K; Abramson, JJ

Published Date

  • July 2003

Published In

Volume / Issue

  • 285 / 1

Start / End Page

  • C215 - C221

PubMed ID

  • 12646413

Pubmed Central ID

  • 12646413

Electronic International Standard Serial Number (EISSN)

  • 1522-1563

International Standard Serial Number (ISSN)

  • 0363-6143

Digital Object Identifier (DOI)

  • 10.1152/ajpcell.00034.2002


  • eng