Assessment of mitochondrial dysfunction arising from treatment with hepatotoxicants.
Assessment of mitochondrial dysfunction arising from treatment with hepatotoxicants.
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评估肝毒药物治疗引起的线粒体功能障碍。
DOI：
10.1002/0471140856.tx1408s44
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Bailey,ShannonM
中科院分区：
文献类型：
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作者：
King,AdrienneL;Bailey,ShannonM
毒物引起的线粒体功能障碍被认为是许多肝脏疾病（包括脂肪性肝炎、肝硬化和癌症）发展的致病因素。毒素介导的线粒体损伤导致ATP产生抑制，无法维持适当的细胞钙稳态，并增加活性氧的产生。这些破坏导致肝细胞死亡并导致肝脏病理学。在此，我们描述了一系列基本和先进的方法，可以纳入旨在了解线粒体功能障碍在毒物诱导的肝毒性中的作用的研究项目。协议提供了分离的肝线粒体，呼吸功能的评估，线粒体钙摄取的测量，和活性氧的生产，以及线粒体蛋白巯基蛋白质组的表征，使用2D凝胶电泳。从这些方法中获得的数据可以整合到一个逻辑和机制框架中，以促进对线粒体功能障碍在毒物诱导的肝脏疾病发病机制中的作用的理解。方案毒理学. 44：14.8.1 - 14.8.29。© 2010年由约翰威利父子公司。
Mitochondrial dysfunction from toxicants is recognized as a causative factor in the development of numerous liver diseases including steatohepatitis, cirrhosis, and cancer. Toxicant‐mediated damage to mitochondria result in depressed ATP production, inability to maintain proper cellular calcium homeostasis, and increased reactive oxygen species production. These disruptions contribute to hepatocellular death and lead to liver pathology. Herein, we describe a series of basic and advanced methodologies that can be incorporated into research projects aimed to understand the role of mitochondrial dysfunction in toxicant‐induced hepatotoxicity. Protocols are provided for isolation of liver mitochondria, assessment of respiratory function, measurement of mitochondrial calcium uptake, and reactive oxygen species production, as well as characterization of the mitochondrial protein thiol proteome using 2D gel electrophoresis. Data obtained from these methods can be integrated into a logical and mechanistic framework to advance understanding of the role of mitochondrial dysfunction in the pathogenesis of toxicant‐induced liver diseases.Curr. Protoc. Toxicol. 44:14.8.1‐14.8.29. © 2010 by John Wiley & Sons, Inc.