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  • Disrupted calcium homeostasis is involved in elevated zinc ion-induced photoreceptor cell death.

Disrupted calcium homeostasis is involved in elevated zinc ion-induced photoreceptor cell death.

Archives of biochemistry and biophysics (2014-07-23)
Dadong Guo, Yuxiang Du, Qiuxin Wu, Wenjun Jiang, Hongsheng Bi
ABSTRACT

Zinc (Zn), the second abundant trace element in living organisms, plays an important role in regulating cell metabolism, signaling, proliferation, gene expression and apoptosis. Meanwhile, the overload of Zn will disrupt the intracellular calcium homeostasis via impairing mitochondrial function. However, the specific molecular mechanism underlying zinc-induced calcium regulation remains poorly understood. In the present study, using zinc chloride (ZnCl2) as a stressor, we investigated the effect of exogenous Zn(2+) in regulating murine photoreceptor cell viability, reactive oxygen species (ROS), cell cycle distribution and calcium homeostasis as well as plasma membrane calcium ATPase (PMCA) isoforms (PMCA1 and PMCA2, i.e., ATP2B1, ATP2B2) expression. We found that the exogenous Zn(2+) in the exposure range (31.25-125.0 μmol/L) results in the overgeneration of ROS, cell cycle arrest at G2/M phases, elevation of cytosolic [Ca(2+)], inactivation of Ca(2+)-ATPase and reduction of both PMCA1 and PMCA2 in 661 W cells, and thus induces cell death. In conclusion, ZnCl2 exposure can elevate the cytosolic [Ca(2+)], disrupt the intracellular calcium homeostasis, further initiate Ca(2+)-dependent signaling pathway in 661 W cells, and finally cause cell death. Our results will facilitate the understanding of cell death induced by the zinc ion-mediated calcium homeostasis disruption.

MATERIALS
Product Number
Brand
Product Description

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