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

• Type of Material: Article
• Authors: Jeffrey S. Otis, Emory University; Lou Ann Brown, Emory University; David M Guidot, Emory University
• Language: English
• Date: 2007-12
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Wiley Periodicals, Inc.
• Final Published Version (URL): http://onlinelibrary.wiley.com/doi/10.1002/mus.20883/abstract
• Title of Journal or Parent Work: Muscle and Nerve
• ISSN: 0148-639X
• Volume: 36
• Issue: 6
• Start Page: 842
• End Page: 848
• Grant/Funding Information: 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: oxidative stress; transforming growth factor-β1; atrogin-1; alcoholic myopathy; glutathione
• Research Categories: Chemistry, Biochemistry; Health Sciences, General

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.