Skeletal muscle protease activities are unaltered in cirrhotic rats but altered in response to ethanol and acetaldehyde in vitro.

Skeletal muscle protease activities are unaltered in cirrhotic rats but altered in response to ethanol and acetaldehyde in vitro.
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DOI:
10.1093/oxfordjournals.alcalc.a045715
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发表时间:
1995-03
影响因子:
2.8
通讯作者:
E. Cook;C. Gove;M. Panos;R. Williams;V. Preedy
E. Cook;C. Gove;M. Panos;R. Williams;V. Preedy
中科院分区:
医学3区
文献类型:
--
作者:
E. Cook;C. Gove;M. Panos;R. Williams;V. Preedy

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本研究试图区分酒精性肝病的肌病中肝损害的贡献和酒精的直接作用。使用肝硬变的动物模型,我们先前已经证明,肌肉中的蛋白质合成潜力没有显着改变。因此,我们调查了肌肉退化增加的可能性。雄性大鼠饮水中加入苯巴比妥钠后,四氯化碳灌胃诱发大鼠肝硬变。对照组只服用苯巴比妥。135天后,组织蛋白酶B和组织蛋白酶D的游离酶活性、潜伏期活性和总活性与组织湿重、蛋白质和DNA的相对表达均未受实验性肝硬变的影响。在正常大鼠和肝硬变大鼠的腓肠肌中也检测到非溶酶体酶中性蛋白酶。自由活动、潜伏活动和总活动两组间差异无统计学意义。在某些情况下,在测定混合物中加入乙醇和乙醛显著改变了肝硬变组织潜伏室和游离室中的蛋白酶的相对活性。在对照组织中,出现了不同的反应模式。结论:在肝硬变中,至少在四氯化碳诱导的大鼠模型中,腓肠肌组织蛋白酶B和D的活性以及中性蛋白酶活性没有变化。乙醇及其代谢物乙醛对潜伏性和游离型肌肉蛋白水解酶活性的影响很小,但很显著。
This study was carried out in an attempt to differentiate between the contribution of liver impairment and direct actions of alcohol in myopathy of alcoholic liver disease. Using an animal model of cirrhosis we have previously shown that protein synthetic potential in muscle was not significantly altered. We therefore investigated the possibility that muscle degradation is increased. Cirrhosis was induced by carbon tetrachloride gavage in male rats receiving phenobarbitone in their drinking water. Controls were given phenobarbitone alone. After 135 days the free, latent and total activities of the lysosomal enzymes cathepsin B and cathepsin D in gastrocnemius muscle were unaffected by the induction of experimental cirrhosis when expressed relative to tissue wet weight, protein or DNA. The non-lysosomal enzyme neutral protease was also measured in gastrocnemius muscle from control and cirrhotic rats. There was no difference between the two groups in the free, latent or total activities. Addition of ethanol and acetaldehyde to the assay mixtures in some cases significantly altered the relative activities of the proteases in latent and free compartments of the cirrhotic tissues. In control tissues a different pattern of response emerged. It is concluded that in cirrhosis, at least in the carbon tetrachloride-induced rat model, there is no change of the activity of cathepsin B and D and the neutral protease activity in gastrocnemius. Small but significant effects of ethanol and its metabolite acetaldehyde on latent and free muscle protease activity were demonstrated.