Hypoxia-induced reactive oxygen species formation in skeletal muscle

J Appl Physiol (1985). 2007 Jun;102(6):2379-88. doi: 10.1152/japplphysiol.01298.2006. Epub 2007 Feb 8.


The existence of hypoxia-induced reactive oxygen species (ROS) production remains controversial. However, numerous observations with a variety of methods and in many cells and tissue types are supportive of this idea. Skeletal muscle appears to behave much like heart in that in the early stages of hypoxia there is a transient elevation in ROS, whereas in chronic exposure to very severe hypoxia there is evidence of ongoing oxidative stress. Important remaining questions that are addressed in this review include the following. Are there levels of PO2 in skeletal muscle, typical of physiological or mildly pathophysiological conditions, that are low enough to induce significant ROS production? Does the ROS associated with muscle contractile activity reflect imbalances in oxygen uptake and demand that drive the cell to a more reduced state? What are the possible molecular mechanisms by which ROS may be elevated in hypoxic skeletal muscle? Is the production of ROS in hypoxia of physiological significance, both with respect to cell signaling pathways promoting cell function and with respect to damaging effects of long-term exposure? Discussion of these and other topics leads to general conclusions that hypoxia-induced ROS may be a normal physiological response to imbalance in oxygen supply and demand or environmental stress and may play a yet undefined role in normal response mechanisms to these stimuli. However, in chronic and extreme hypoxic exposure, muscles may fail to maintain a normal redox homeostasis, resulting in cell injury or dysfunction.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Hypoxia
  • Humans
  • Hypoxia / physiopathology*
  • Models, Biological*
  • Muscle Contraction*
  • Muscle, Skeletal / physiopathology*
  • Oxidative Stress
  • Oxygen / metabolism*
  • Oxygen Consumption*
  • Reactive Oxygen Species / metabolism*


  • Reactive Oxygen Species
  • Oxygen