Publication Date:
2015-12-18
Description:
ABSTRACT Calcium (Ca 2+ ) is a ubiquitous cell signal responsible for multiple fundamental cellular functions, including apoptosis. Whether the homeostasis of Ca 2+ is involved in arsenite-induced apoptosis remains unclear. In this study, we observed that arsenite significantly elevated the intracellular Ca 2+ concentration in a dose- and time-dependent manner. By using the Ca 2+ -ATPase inhibitor, thapsigargin, and the inositol 1,4,5- trisphosphate receptors (IP3Rs) inhibitor, heparin, we further confirmed that the disturbance of endoplasmic reticulum (ER) Ca 2+ homeostasis caused Ca 2+ overload in the cells. Moreover, loss of ER Ca 2+ homeostasis also led to ER stress, mitochondrial dysfunction, and NF-κB activation. Importantly, pretreatment of cells with heparin remarkably attenuated the elevated cell apoptosis induced by arsenite, but inhibition of ER Ca 2+ uptake with thapsigargin exacerbated arsenite-induced cell damage significantly. Together, we demonstrated for the first time that arsenite disturbed the Ca 2+ homeostasis in ER, which subsequently led to ER stress, mitochondrial dysfunction, and NF-κB nuclear translocation, and thus consequently triggering cell apoptosis. Our findings indicate regulation of disrupted Ca 2+ homeostasis in ER may be a potential strategy for prevention of arsenite toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.
Print ISSN:
1520-4081
Electronic ISSN:
1522-7278
Topics:
Energy, Environment Protection, Nuclear Power Engineering
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