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Nickel sulfate induced apoptosis via activating ROS‐dependent mitochondria and endoplasmic reticulum stress pathways in rat Leydig cells
Author(s) -
Zou Lingyue,
Su Li,
Sun Yifan,
Han Aijie,
Chang Xuhong,
Zhu An,
Liu Fangfang,
Li Jin,
Sun Yingbiao
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22414
Subject(s) - apoptosis , endoplasmic reticulum , microbiology and biotechnology , mitochondrion , reactive oxygen species , annexin , cytochrome c , unfolded protein response , chemistry , oxidative stress , biology , biochemistry
Abstract Nickel can induce apoptosis of testicular Leydig cells in mice, whereas the mechanisms remain unclear. In this study, we investigated the role of nickel‐induced reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum stress (ERS) mediated apoptosis pathways in rat Leydig cells. Fluorescent DCF and Annexin‐V FITC/PI staining were performed to measure the production of ROS and apoptosis in Leydig cells. RT‐qPCR and Western blot were conducted to analyze the key genes and proteins involved in mitochondria and ERS apoptotic pathways. The results showed that nickel sulfate induced ROS generation, consequently resulted in nucleolus deformation and apoptosis in testicular Leydig cells, which were then attenuated by ROS inhibitors of N ‐acetylcysteine (NAC) and 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO). Nickel sulfate‐triggered Leydig cells apoptosis via mitochondria and ERS pathways was characterized by the upregulated mRNA and proteins expression of Bak, cytochrome c , caspase 9, caspase 3, GRP78, GADD153, and caspase 12, which were inhibited by NAC and TEMPO respectively. The findings indicated that nickel‐induced ROS generation was involved in apoptosis via mitochondria and ERS pathways in rat Leydig cells.