期刊
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
卷 205, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2020.111326
关键词
Hexavalent chromium [Cr(VI)]; Clusterin; Mitochondrial apoptosis; Reactive oxygen species (ROS); Dynamin-related protein 1 (Drp1); AMP-Activated protein kinase (AMPK)
资金
- National Natural Science Foundation of China [81773478]
- Natural Science Fund for Excellent Young Scholars of Hunan Province, China [2020JJ3052]
Hexavalent chromium [Cr(VI)] is ubiquitous in the environment and is commonly used in various industrial processes. Clusterin (CLU) is an extracellular chaperone protein which exerts the anti-apoptotic function. In this study, we aimed to explore the effect of CLU on Cr(VI)-induced mitochondrial fission and apoptosis. We revealed that the apoptosis rate of L02 hepatocytes treated with Cr (VI) was increased. CLU over-expression could protect the hepatocytes from Cr(VI)-induced mitochondrial apoptosis. Furthermore, Cr(VI) triggered the intracellular calcium overload, resulting in the activation of xanthine oxidase (XO). Cr(VI) induced reactive oxygen species (ROS) overproduction, led to dynamin-related protein 1 (Drp1) translocation to mitochondria and the subsequent mitochondrial fission, contributing to the caspase-3-dependent mitochondrial apoptosis as evidenced by higher mitochondrial permeability transition pore (mPTP) opening rate, lower mitochondrial membrane potential (MMP), and more alanine transaminase (ALT)/aspartate transaminase (AST) leakage into the culture medium. However, CLU over-expression could trigger the AMP-activated protein kinase (AMPK) pathway, which was followed by the increase of sarcoplasmic reticulum Ca2+ -ATPase (SERCA2a) expression. CLU-induced AMPK/SERCA2a activation attenuated calcium overload, caspase-3 activation, and ultimate mitochondrial apoptosis. All in all, the present study demonstrated that Cr(VI) induced hepatocytes apoptosis via Ca2+-ROS-Drp1-mitochondria' fission axis and CLU alleviated the mitochondrial apoptosis through activation of the AMPK/SERCA2a pathway.
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