Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats.
Procysteine stimulates expression of key anabolic factors and reduces plantaris atrophy in alcohol-fed rats.
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DOI：
10.1111/j.1530-0277.2009.00975.x
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发表时间：
2009-08
期刊：
影响因子：
--
通讯作者：
Guidot DM
中科院分区：
文献类型：
--
作者：
Otis JS;Guidot DM
长期饮酒可能会产生严重的氧化应激，并导致骨骼肌功能障碍。越来越多的证据表明，白介素6(IL-6)家族的细胞因子在骨骼肌群调节中发挥着不同的作用。因此，我们的目标是(1)通过在酒精喂养的大鼠的饮食中补充谷胱甘肽前体原半胱氨酸来最小化氧化应激的程度和减轻萎缩，以及(2)确定IL-6家族成员在酒精性肌病中的作用。年龄和性别匹配的Spraogue-Dawley大鼠被喂以含有酒精或等卡路里替代品的Lieber-DeCarli液体饮食(对照饮食)35wk。酒精喂养的各亚组大鼠在最后12周内给予原半胱氨酸(0.35%，w/v)。用苏木精-伊红染色观察足底形态。用试剂盒检测谷胱甘肽代谢的主要成分。用实时荧光定量聚合酶链式反应(Real Time PCR)检测几个基因的表达水平。酒精喂养的大鼠足底肌肉出现广泛萎缩，谷胱甘肽水平降低，谷胱甘肽还原酶和谷胱甘肽过氧化物酶活性降低，超氧化物歧化酶-2(Mn-SOD2)活性降低，NADPH氧化酶-1基因表达增加--这都是显著的氧化应激的迹象。酒精还可诱导分解代谢因子的基因表达，包括IL-6、抑癌素M、阿托金-1、肌肉环指蛋白-1和IGFBP-1。丙半胱氨酸处理减轻了足底萎缩，恢复了谷胱甘肽水平，增加了过氧化氢酶、铜/锌-SOD1和锰-SOD2mRNA的表达，但没有降低氧化应激的其他标志或这些分解代谢因子的水平。相反，原半胱氨酸刺激了合成代谢因子的基因表达，如胰岛素样生长因子-1、睫状神经营养因子和心肌营养素-1。丙半胱氨酸显著减弱，但不能完全消除酒精引起的氧化应激或分解代谢因子。相反，原半胱氨酸通过诱导几种合成代谢途径的成分来最大限度地减少足底萎缩的程度。因此，抗氧化剂治疗，如补充原半胱氨酸，可能会使酒精性肌病患者受益。
Long term alcohol ingestion may produce severe oxidant stress and lead to skeletal muscle dysfunction. Emerging evidence has suggested that members of the interleukin-6 (IL-6) family of cytokines play diverse roles in the regulation of skeletal muscle mass. Thus, our goals were (1) to minimize the degree of oxidant stress and attenuate atrophy by supplementing the diets of alcohol-fed rats with the glutathione precursor, procysteine, and (2) to identify the roles of IL-6 family members in alcoholic myopathy. Age- and gender-matched Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet containing either alcohol or an isocaloric substitution (control diet) for 35 wk. Subgroups of alcohol-fed rats received procysteine (0.35%, w/v) for the final 12 wk. Plantaris morphology was assessed by hematoxylin and eosin staining. Major components of glutathione metabolism were determined by assay kits. Real time PCR was used to determine expression levels of several genes. Plantaris muscles from alcohol-fed rats displayed extensive atrophy, as well as decreased glutathione levels, decreased activities of glutathione reductase and glutathione peroxidase, decreased superoxide dismutase (SOD)-2 (Mn-SOD2), and increased NADPH oxidase-1 gene expression - each indicative of significant oxidant stress. Alcohol also induced gene expression of catabolic factors including IL-6, oncostatin M, atrogin-1, muscle ring finger protein-1, and IGFBP-1. Procysteine treatment attenuated plantaris atrophy, restored glutathione levels, and increased catalase, Cu/Zn-SOD1, and Mn-SOD2 mRNA expression, but did not reduce other markers of oxidant stress or levels of these catabolic factors. Instead, procysteine stimulated gene expression of anabolic factors such as insulin-like growth factor-1, ciliary neurotrophic factor and cardiotrophin-1. Procysteine significantly attenuated, but did not completely abrogate, alcohol-induced oxidant stress or catabolic factors. Rather, procysteine minimized the extent of plantaris atrophy by inducing components of several anabolic pathways. Therefore, anti-oxidant treatments such as procysteine supplementation may benefit individuals with alcoholic myopathy.
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影响因子：
3.3
作者：
Fernández-Solà, J;Nicolás, JM;Urbano-Márquez, A
通讯作者：
Urbano-Márquez, A
DOI：
10.1097/00000374-199806000-00008
发表时间：
1998-06-01
影响因子：
3.2
作者：
Lang, CH;Fan, J;McDonough, KH
通讯作者：
McDonough, KH
影响因子：
4.8
作者：
Kim, Hyuck;Jo, Chulman;Jo, Sangmee Ahn
通讯作者：
Jo, Sangmee Ahn
DOI：
10.1097/00000374-200212000-00013
发表时间：
2002-12-01
影响因子：
3.2
作者：
Fernández-Solà, J;García, G;Nicolás, JM
通讯作者：
Nicolás, JM
DOI：
10.1152/ajpendo.00181.2002
发表时间：
2002-11-01
影响因子：
5.1
作者：
Kumar, V;Frost, RA;Lang, CH
通讯作者：
Lang, CH