PMID- 29248592 OWN - NLM STAT- MEDLINE DCOM- 20180918 LR - 20180918 IS - 1879-3177 (Electronic) IS - 0887-2333 (Linking) VI - 47 DP - 2018 Mar TI - Fluorochloridone induces primary cultured Sertoli cells apoptosis: Involvement of ROS and intracellular calcium ions-mediated ERK1/2 activation. PG - 228-237 LID - S0887-2333(17)30372-7 [pii] LID - 10.1016/j.tiv.2017.12.006 [doi] AB - Fluorochloridone (FLC) is a widely used pyrrolidone selective herbicide and reported to induce testis injuries in male rats, but the underlying mechanism is largely unknown. In the present study, primary-cultured Sertoli cells were exposed to FLC at the concentration of 0-10.00muM to study the mechanism of FLC-induced apoptosis. The roles of ROS, intracellular calcium, endoplasmic reticulum (ER), and ERK1/2 were looked at with ROS scavenger N-acetyl-cysteine (NAC), intracellular calcium chelator BAPTA-AM, ER calcium depleting agent thapsigargin (TG), and ERK1/2 inhibitor U0126, respectively. FLC induced dose-dependent apoptosis increase as well as the elevation in levels of ROS, intracellular calcium, and ERK1/2 activation. FLC treatment led to constantly increasing apoptotic rates and ERK1/2 activation over time, while inversed-V shaped change tendencies of ROS and intracellular calcium levels were observed. FLC-induced ROS generation disrupted the intracellular calcium homeostasis by attacking the ER, and the elevated intracellular calcium levels resulted in ERK1/2 over-phosphorylation and consequently promoted Sertoli cell apoptosis. Taken together, ROS and intracellular calcium-mediated ERK1/2 activation led to FLC-induced Sertoli cell apoptosis. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Liu, Luqing AU - Liu L AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. FAU - Chang, Xiuli AU - Chang X AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. FAU - Zhang, Yubin AU - Zhang Y AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. FAU - Wu, Chunhua AU - Wu C AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. FAU - Li, Rui AU - Li R AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China; Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. FAU - Tang, Liming AU - Tang L AD - Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai 201203, China. FAU - Zhou, Zhijun AU - Zhou Z AD - School of Public Health/MOE Key Laboratory for Public Health Safety/Collaborative Innovation Center of Social Risks Governance in Health, Fudan University, Shanghai 200032, China. Electronic address: zjzhou@fudan.edu.cn. LA - eng PT - Journal Article DEP - 20171214 PL - England TA - Toxicol In Vitro JT - Toxicology in vitro : an international journal published in association with BIBRA JID - 8712158 RN - 0 (Antioxidants) RN - 0 (Calcium Chelating Agents) RN - 0 (Enzyme Inhibitors) RN - 0 (Herbicides) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Pyrrolidinones) RN - 0 (Reactive Oxygen Species) RN - AO023ZB1BP (raiser) RN - EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Apoptosis/*drug effects MH - Calcium Chelating Agents/pharmacology MH - Calcium Signaling/*drug effects MH - Cell Survival/drug effects MH - Cells, Cultured MH - Endoplasmic Reticulum/drug effects/enzymology/metabolism MH - Enzyme Activation/drug effects MH - Enzyme Inhibitors/pharmacology MH - Herbicides/*toxicity MH - Hormesis MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Phosphorylation/drug effects MH - Protein Kinase Inhibitors/pharmacology MH - Protein Processing, Post-Translational/drug effects MH - Pyrrolidinones/*toxicity MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/*metabolism MH - Sarcoplasmic Reticulum Calcium-Transporting ATPases/antagonists & inhibitors/metabolism MH - Sertoli Cells/cytology/*drug effects OTO - NOTNLM OT - Apoptosis OT - ERK1/2 OT - Fluorochloridone OT - Intracellular calcium OT - ROS EDAT- 2017/12/19 06:00 MHDA- 2018/09/19 06:00 CRDT- 2017/12/18 06:00 PHST- 2017/08/03 00:00 [received] PHST- 2017/11/18 00:00 [revised] PHST- 2017/12/12 00:00 [accepted] PHST- 2017/12/19 06:00 [pubmed] PHST- 2018/09/19 06:00 [medline] PHST- 2017/12/18 06:00 [entrez] AID - S0887-2333(17)30372-7 [pii] AID - 10.1016/j.tiv.2017.12.006 [doi] PST - ppublish SO - Toxicol In Vitro. 2018 Mar;47:228-237. doi: 10.1016/j.tiv.2017.12.006. Epub 2017 Dec 14.