内质网应激在镉致鲤鱼上皮瘤细胞自噬中的调节机制

项目名称： 内质网应激在镉致鲤鱼上皮瘤细胞自噬中的调节机制

项目编号： No.31460696

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 农业科学

项目作者： 高典

作者单位： 南昌大学

项目金额： 52万元

中文摘要： 镉作为一种重要的、广泛存在于水环境中的重金属污染物，其导致的动物机体损伤已受到人们的高度重视，但相关的细胞毒性机制尚未明确。我们的前期研究结果表明，镉除了诱导鲤鱼细胞凋亡外，还可诱导细胞自噬。鉴于自噬在维持细胞内环境稳态中的重要作用，并结合镉诱导鲤鱼自噬发生时，内质网应激伴侣分子GRP78蛋白水平上调和胞内钙离子水平升高的现象，我们推测：自噬在镉胁迫产生的细胞毒性反应中发挥重要调控作用，内质网应激参与了自噬发生的调控。本项目拟以鲤鱼上皮瘤细胞作为研究对象，通过研究镉诱导的自噬及抑制自噬对细胞增殖、凋亡和死亡的影响，明确镉诱导自噬与细胞存活的关系；通过探讨镉诱导未折叠蛋白反应、钙离子的释放及抑制相关反应和信号通路分子对自噬的影响，阐明内质网应激在镉诱导自噬发生过程中的调控机理。本研究为揭示鱼类自噬的生理功能、理解镉胁迫下的细胞毒性调控机制奠定基础，为制定相应的防治对策提供理论依据。

中文关键词： 细胞自噬；镉；鲤鱼；内质网应激；细胞凋亡

英文摘要： As an important heavy metal pollutant, cadmium (Cd) is widely distributed in water. Although people have payed attention to the serious body injury-reaction caused by Cd, the related cytotoxic mechanism has not been elucidated absolutely. Our prevous studies show that Cd can induce epithelioma papulosum cyprini (EPC) cell autophagy besides that it can induce cell apoptosis. According the fact that autophagy play an immportant role in maintaining cellular homeostasis and the protein level of glucose-regulated protein 78 (GRP78) and calcium levels were up-regulated when EPC cell autophagy was triggered by Cd, we speculate that autophagy plays a critical role in Cd-induced cytotoxic reaction and ERS participates in the regulatory function of autophagosome information. In the present study, EPC cell line will be be used as a in vitro model. The aim of this study is to elucidate the relationship between autophagy and cell survival through detecting changes of cell proliferation, apoptosis and necrosis when autophagy is induced by Cd and inhibited. Furthermore, to explore the regulatory mechanism of ERS in Cd-induced autophagy, we will determine the effects of unfolded protein response and calcium release to autophagy. The findings from the proposed study will be helpful to understand the physiological function of fish autophagy and represent the regulatory mechanism of the cytotoxic effects of cadmium. Moreover, it will also provide theoretical foundation to prevent and control the disease caused by Cd exposure.

英文关键词： autophagy;cadmium;common carp;endoplasmic reticulum stress;apoptosis