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Author Notes:

Correspondence: J. S. Otis, Pulmonary, Allergy and Critical Care Medicine, Atlanta VA Medical Center and Emory University School of Medicine, 1670 Clairmont Road, 12C-191, Decatur, Georgia 30033, USA; Email: jsotis@emory.edu.

Subjects:

Research Funding:

This work was supported by Grant AR052255-02 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (to J.S.O.) and by Grant P-50 AA013757 from the National Institute on Alcohol Abuse and Alcoholism (to D.M.G.).

Keywords:

  • alcoholic myopathy
  • atrogin-1
  • glutathione
  • oxidative stress
  • transforming growth factor-β1

Oxidant-induced atrogin-1 and transforming growth factor-β1 precede alcohol-related myopathy in rats

Tools:

Journal Title:

Muscle and Nerve

Volume:

Volume 36, Number 6

Publisher:

, Pages 842-848

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Alcohol-related chronic myopathy is characterized by severe biochemical and structural changes to skeletal muscle. Our goals were to: (1) identify early regulatory elements that precede the overt manifestation of plantaris atrophy; and (2) circumvent these derangements by supplementing alcohol-fed rats with the glutathione precursor, procysteine. After 6 weeks of daily ingestion, before the development of overt atrophy of the plantaris muscle, alcohol increased several markers of oxidative stress and increased gene expressions of atrogin-1 and transforming growth factor-β1 (TGF-β1) by ~60- and ~65-fold, respectively, which were attenuated by procysteine supplementation. Interestingly, after 28 weeks of alcohol ingestion, when overt plantaris atrophy had developed, atrogin-1 and TGF-β1 gene expression had returned to baseline levels. Together, these findings suggest that alcohol-induced, redox-sensitive alterations drive pro-atrophy signaling pathways that precede muscle atrophy. Therefore, targeted anti-oxidant treatments such as procysteine supplementation may benefit individuals with chronic alcohol abuse, particularly if given prior to the development of clinically significant myopathy.

Copyright information:

© 2007 Wiley Periodicals, Inc.

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