The Pivotal Role of Ca²⁺ Homeostasis in PBDE-47-Induced Neuronal Apoptosis

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• 作者：Shun Zhang ; Yihu Chen ; Xue Wu ; Hui Gao ; Rulin Ma ; Chunyang Jiang…
• 关键词：PBDE ; 47 ; Neurotoxicity ; Apoptosis ; [Ca2+]i ; ΔΨm
• 刊名：Molecular Neurobiology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：53
• 期：10
• 页码：7078-7088
• 全文大小：4,981 KB
• 刊物主题：Neurosciences; Neurobiology; Cell Biology; Neurology;
• 出版者：Springer US
• ISSN：1559-1182
• 卷排序：53

文摘

Polybrominated diphenyl ethers (PBDEs) are widely used flame retardants and are ubiquitous in the environment and human tissues. Recent evidence has demonstrated that PBDE-induced neurotoxicity is associated with neuronal apoptosis via interfering with the calcium ion (Ca2+) homeostasis; however, the underlying mechanisms remain elusive. Thus, we sought to investigate the role of Ca2+ homeostasis in PBDE-47-induced neuronal apoptosis. Here, we showed that PBDE-47 significantly decreased neuronal number while increased neuronal apoptosis in vitro and in vivo, as manifested by an increased percentage of Annexin V-positive staining cells and caspase-3 activation in human neuroblastoma SH-SY5Y cells and hippocampal neurons of rats. Further study identified that PBDE-47 elicited ΔΨ_m collapse following an early and sustained [Ca2+]_i, overload, as well as stimulated cytochrome c release from mitochondria into the cytosol in SH-SY5Y cells and rat hippocampal tissue. Interestingly, the extracellular Ca2+ chelator ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA) blocked PBDE-47-induced [Ca2+]_i elevation, ΔΨ_m collapse, cytochrome c release, and caspase-3 activation in SH-SY5Y cells, whereas the intracellular Ca2+ chelator 1,2-bis (2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) had no influences on them, indicating that the [Ca2+]_i overload originates primarily from extracellular Ca2+ component rather than from intracellular calcium storage and that the increase in [Ca2+]_i is a major contributor to ΔΨ_m collapse and subsequent neuronal apoptosis. Overall, these findings suggest that PBDE-47 affects Ca2+ homeostasis as a crucial event in activation of neuronal death associated with mitochondria and provide novel insight into the mechanism of action underlying PBDE neurotoxicity.