title: Nickel sulfate induced apoptosis via activating ROS-dependent mitochondria and endoplasmic reticulum stress pathways in rat Leydig cells.
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.
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Lingyue
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Aijie
authors.initials: A
authors.lastname: Han
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Chang
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: An
authors.initials: A
authors.lastname: Zhu
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, 730000, China.
authors.forename: Yingbiao
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000378:metabolism; D007985:Leydig Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009532:Nickel / Q000633:toxicity*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D003497:Cyclic N-Oxides; C497251:Ddit3 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D017382:Reactive Oxygen Species; D051742:Transcription Factor CHOP; C029938:nickel sulfate; D009532:Nickel; D045304:Cytochromes c; D053454:Caspase 12; D053148:Caspase 3; D053453:Caspase 9; C003959:TEMPO; D000111:Acetylcysteine
keywords: Leydig cells; apoptosis; endoplasmic reticulum stress; mitochondria; nickel sulfate; reactive oxygen species