title: Disrupted calcium homeostasis is involved in elevated zinc ion-induced photoreceptor cell death.
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.
authors: Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
authors: Dadong
authors: D
authors: Guo
authors: Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
authors: Yuxiang
authors: Y
authors: Du
authors: Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
authors: Qiuxin
authors: Q
authors: Wu
authors: Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China.
authors: Wenjun
authors: W
authors: Jiang
authors: Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan 250002, China. Electronic address: azuresky1999@163.com.
authors: Hongsheng
authors: H
authors: Bi
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010786:Photoreceptor Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D017967:Zinc Compounds / Q000494:pharmacology*
chemical_list: D002712:Chlorides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D017967:Zinc Compounds; C016837:zinc chloride; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium
keywords: Calcium homeostasis; Cell cycle arrest; Plasma membrane calcium ATPase; Reactive oxygen species; Zinc chloride