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

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. Muscle Nerve, 2007