Angiotensin II, oxidative stress and skeletal muscle wasting.
Angiotensin II, oxidative stress and skeletal muscle wasting.
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DOI：
10.1097/maj.0b013e318222e620
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Delafontaine P
中科院分区：
文献类型：
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作者：
Sukhanov S;Semprun-Prieto L;Yoshida T;Michael Tabony A;Higashi Y;Galvez S;Delafontaine P
肌肉萎缩（恶病质）是一种肌肉消耗综合征，与人类的几种病理状况有关，如充血性心力衰竭、糖尿病、AIDS、癌症和肾衰竭，以及恶病质的存在。许多与恶病质相关的疾病伴随着肾素血管紧张素系统的刺激和血管紧张素II（angII）水平的升高。血管紧张素II输注诱导啮齿动物骨骼肌萎缩，其机制包括E3连接酶atrogin-1/MuRF-1的表达增加，泛素-蛋白酶体介导的蛋白水解速率升高和活性氧（ROS）水平升高，与人类恶病质的状况非常相似。血管紧张素II诱导的氧化应激导致小鼠模型肌肉萎缩。烟酰胺腺嘌呤二核苷酸磷酸氧化酶-和腺苷酸衍生的ROS有助于血管紧张素II诱导的氧化应激。特异性靶向ROS和烟酰胺腺嘌呤二核苷酸磷酸氧化酶/线粒体串扰可能是治疗恶病质的有益的新疗法。
Muscle atrophy (cachexia) is a muscle wasting syndrome associated with several pathological conditions in humans such as congestive heart failure, diabetes, AIDS, cancer and renal failure, and the presence of cachexia worsens outcome. Many of the conditions associated with cachexia are accompanied by stimulation of the reninangiotensin system and elevation in angiotensin II (ang II) levels. Ang II infusion induces skeletal muscle atrophy in rodents and mechanisms include increased expression of the E3 ligases atrogin-1/MuRF-1, an elevated rate of ubiquitin-proteasome mediated proteolysis and increased reactive oxygen species (ROS) levels, closely mimicking conditions of human cachexia. Ang II-induced oxidative stress contributes to muscle atrophy in a mouse model. Nicotinamide adenine dinucleotide phosphate oxidase- and mitochondria-derived ROS contribute to ang II-induced oxidative stress. Specific targeting of ROS and nicotinamide adenine dinucleotide phosphate oxidase/mitochondria cross-talk could be a beneficial, novel therapy to treat cachexia.