Selective protein covalent binding and target organ toxicity
Selective protein covalent binding and target organ toxicity
复制标题
DOI：
10.1006/taap.1996.8074
复制
发表时间：
1997-03-01
影响因子：
3.8
通讯作者：
Hinson, JA
中科院分区：
文献类型：
--
作者：
Cohen, SD;Pumford, NR;Hinson, JA
异种代谢产物与蛋白质的共价结合长期以来一直与靶器官毒性有关，但这种结合的机制尚未得到广泛的证实，现代生化、分子和免疫化学方法有助于识别异种共价结合的特定蛋白质靶点，这些研究表明，蛋白质共价结合不是随机的，而是相对于靶向的蛋白质具有选择性。与总蛋白共价结合相比，选择性结合特定细胞靶蛋白可能与毒性更相关。目前的研究方向是鉴定和鉴定靶蛋白，并阐明这种结合对其结构、功能的影响以及在靶器官毒性中的潜在作用。描述了用于检测和鉴定目标蛋白质的方法，对乙酰氨基酚、氟烷和2，5-己二酮的代谢物形成共价结合的加合物与最近识别的蛋白质靶标。这种选择性结合可能会影响体内平衡或其他细胞反应，进而导致药物毒性、超敏反应或自身免疫。(C)1997年学术出版社。
Protein covalent binding by xenobiotic metabolites has long been associated with target organ toxicity but mechanistic involvement of such binding has not been widely demonstrated, Modern biochemical, molecular, and immunochemical approaches have facilitated identification of specific protein targets of xenobiotic covalent binding, Such studies have revealed that protein covalent binding is not random, but rather selective with respect to the proteins targeted. Selective binding to specific cellular target proteins may better correlate with toxicity than total protein covalent binding. Current research is directed at characterizing and identifying the targeted proteins and clarifying the effect of such binding on their structure, function, and potential roles in target organ toxicity. The approaches employed to detect and identify the targeted proteins are described, Metabolites of acetaminophen, halothane, and 2,5-hexanedione form covalently bound adducts to recently identified protein targets. The selective binding may influence homeostatic or other cellular responses which in turn contribute to drug toxicity, hypersensitivity, or autoimmunity. (C) 1997 Academic Press.