Journal
TOXICOLOGY IN VITRO
Volume 47, Issue -, Pages 228-237Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.tiv.2017.12.006
Keywords
Fluorochloridone; Apoptosis; ROS; Intracellular calcium; ERK1/2
Categories
Funding
- National Natural Science Foundation of China [81373040]
- Shanghai Project 3-Year Action [15GWZK0202, GWIV-27.3]
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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 0-10.00 mu M 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.
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