HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free All Versions of this Article: 102/6/2379    most recent 01298.2006v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Clanton, T. L. Search for Related Content PubMed PubMed Citation Articles by Clanton, T. L.

INVITED REVIEW

HIGHLIGHTED TOPIC
Free Radical Biology in Skeletal Muscle

Hypoxia-induced reactive oxygen species formation in skeletal muscle

Division of Pulmonary, Critical Care, Allergy and Sleep Medicine, Department of Internal Medicine, The Dorothy M. Davis Heart & Lung Research Institute, The Ohio State University College of Medicine, Columbus, Ohio

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.

reduced nicotinamide adenine dinucleotide; free radicals; ischemia; oxidase; mitochondria; exercise; altitude

This article has been cited by other articles:

				M. Mayr, A. Sidibe, and A. Zampetaki The Paradox of Hypoxic and Oxidative Stress in Atherosclerosis J. Am. Coll. Cardiol., April 1, 2008; 51(13): 1266 - 1267. [Full Text] [PDF]

				L. F. Ferreira and M. B. Reid Muscle-derived ROS and thiol regulation in muscle fatigue J Appl Physiol, March 1, 2008; 104(3): 853 - 860. [Abstract] [Full Text] [PDF]

				S. Aydin, S. Signorelli, T. Lechleitner, M. Joannidis, C. Pleban, P. Perco, W. Pfaller, and P. Jennings Influence of microvascular endothelial cells on transcriptional regulation of proximal tubular epithelial cells Am J Physiol Cell Physiol, February 1, 2008; 294(2): C543 - C554. [Abstract] [Full Text] [PDF]

				Y. Lecarpentier Physiological role of free radicals in skeletal muscles J Appl Physiol, December 1, 2007; 103(6): 1917 - 1918. [Full Text] [PDF]

				K. A. Sanders and J. R. Hoidal The NOX on Pulmonary Hypertension Circ. Res., August 3, 2007; 101(3): 224 - 226. [Full Text] [PDF]