Oxidant-induced atrogin-1 and transforming growth factor-β1 precede alcohol-related myopathy in rats
Oxidant-induced atrogin-1 and transforming growth factor-β1 precede alcohol-related myopathy in rats
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DOI：
10.1002/mus.20883
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发表时间：
2007-12-01
期刊：
影响因子：
3.4
通讯作者：
Guidot, David M.
中科院分区：
文献类型：
--
作者：
Otis, Jeffrey S.;Brown, Lou Ann S.;Guidot, David M.
酒精相关的慢性肌病以骨骼肌严重的生化和结构改变为特征。我们的目标是：(1)确定在植物萎缩明显表现之前的早期调控因素；(2)通过给酒精喂养的大鼠补充谷胱甘肽前体半胱氨酸来避免这些紊乱。每天摄入6周后，在跖肌出现明显萎缩之前，酒精增加了几种氧化应激标志物，并增加了atrogenin -1和转化生长因子- β 1 （tgf - β 1）的基因表达，分别增加了大约60倍和65倍，而补充半胱氨酸可以减轻这种作用。有趣的是，在摄入酒精28周后，当明显的跖萎缩发生时，萎缩素-1和tgf - β 1基因的表达已经恢复到基线水平。总之，这些发现表明，酒精诱导的氧化还原敏感改变驱动肌肉萎缩前的促萎缩信号通路。因此，有针对性的抗氧化治疗，如补充半胱氨酸，可能对慢性酒精滥用患者有益，特别是在出现临床显著肌病之前给予治疗。
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-beta 1 (TGF-beta 1) by similar to 60- and similar to 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-beta 1 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.