Cytokines and oxidative signalling in skeletal muscle.
A growing body of literature indicates that cytokines regulate skeletal muscle function, including gene expression and adaptive responses. Tumour necrosis factor-alpha (TNF-alpha) is the cytokine most prominently linked to muscle pathophysiology and, therefore, has been studied most extensively in muscle-based systems. TNF-alpha is associated with muscle catabolism and loss of muscle function in human diseases that range from cancer to heart failure, from arthritis to AIDS. Recent advances have established that TNF-alpha causes muscle weakness via at least two mechanisms, accelerated protein loss and contractile dysfunction. Protein loss is a chronic response that occurs over days to weeks. Changes in gene expression required for TNF-alpha induced catabolism are regulated by the transcription factor nuclear factor-kappaB which is essential for the net loss of muscle protein caused by chronic TNF-alpha exposure. Contractile dysfunction is an acute response to TNF-alpha stimulation, developing over hours and resulting in decreased force production. Both actions of TNF-alpha involve a rapid rise in endogenous oxidants as an essential step in post-receptor signal transduction. These oxidants appear to include reactive oxygen species derived from mitochondrial electron transport. Such information provides insight into the cellular and molecular mechanisms of TNF-alpha action in skeletal muscle and establishes a scientific basis for continued research into cytokine signalling.
Reid
M B
MB
Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Li
Y P
YP
D000818:Animals; D006801:Humans; D051379:Mice; D024510:Muscle Development; D018908:Muscle Weakness / Q000209:etiology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development / Q000502:physiology*; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha