内质网应激与金属毒作用机制关系的研究进展  

Research Advance on Relationship between Endoplasmic Reticulum Stress and Metal Toxicity

作　　者：张叶[1] 蒋旭超[1] 钱海[1] 马静[1] 陆荣柱[1] 

机构地区：[1]江苏大学基础医学与医学技术学院预防医学系,江苏镇江212013

出　　处：《环境与健康杂志》2010年第10期922-925,共4页Journal of Environment and Health

基　　金：国家自然科学基金资助项目(30872139);江苏大学营养与疾病科研团队基金资助项目(2008);江苏大学大学生科研立项项目(08A039)

摘　　要：内质网应激是指细胞内质网钙稳态失衡或蛋白质加工运输障碍,生理功能发生紊乱时的一种亚细胞器应答反应,主要表现为未折叠蛋白反应。内质网应激反应是细胞适应的一种自身保护机制,但持续的或剧烈的应激反应却能激发程序性细胞死亡。内质网应激可以由多种干扰内质网功能的病理生理改变以及其他环境因素变化引起,金属化学物也是重要的诱发内质网应激的外界环境因素。内质网应激作为一种适应和保护机制,研究内质网应激在金属毒性中的作用有助于探讨毒作用机制和化学防护剂的开发。本研究在描述内质网应激与铅、镉、汞、铁、锰、铬等金属毒性关系的基础上,发现不同金属诱导内质网应激具有明显的时间效应和剂量效应特点,基本表现为早期诱导,晚期恢复或抑制;低剂量激活,而高剂量抑制。这为探讨金属毒性机制提供给了新的靶点。Endoplasmic reticulum （ER） stress is a special subcellular response when the cell encounters a disturbance of calcium homeostasis, dysfunction of protein processing or transportation or disorder of other cellular function. Among all ER stress responses,unfolded protein response （UPR） is one of the most important ones and extensively explored. Endoplasmic reticulum stress response is a self-protective mechanism for the cell adaptation, but when it is persistent or severe, apoptosis may be induced. Though a variety of disturbances of endoplasmic reticulum function in pathophysiological changes can induce endoplasmic reticulum stress,exposure to environmental chemicals including metals has been recognized as exogenous factor. Due to the dual roles of ER stress in cellular adaptation and self-protection and toxicity exploring the role of ER stress in metal toxicity may contribute to understanding of toxic mechanisms and development of chemopreventive agents. This paper described the relationship between ER stress and metal toxicity such as lead , cadmium , mercury , iron , manganese , chromium. Furthermore,it also showed that almost all metals could induce ER stress with time-dose-response manner. The common phenomenon is that early induction followed by late recovery or inhibition. With regard to dosage, activation of low-dose and inhibition high-dose can also be observed in various metals-treated organisms. These findings are beneficial to looking into new targets for investigating the mechanism of metals toxicity.

关 键 词：内质网应激 未折叠蛋白反应 重金属 

分 类 号：R994.6[医药卫生—毒理学]