The Pivotal Role of Ca2+ Homeostasis in PBDE-47-Induced Neuronal Apoptosis
| Autor: | Rongrong Lei, Chunyang Jiang, Shun Zhang, Gang Kuang, Tao Xia, Yihu Chen, Guodong Zhao, Cheng Zhang, Pei Li, Xue Wu, Aiguo Wang, Hui Gao, Rulin Ma, Xiaofei Zhang, Chunyan Xu |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
biology Cytochrome c Neuroscience (miscellaneous) 010501 environmental sciences Bioinformatics 01 natural sciences Calcium in biology Cell biology 03 medical and health sciences Cellular and Molecular Neuroscience EGTA chemistry.chemical_compound 030104 developmental biology Neurology chemistry BAPTA Apoptosis biology.protein Extracellular reproductive and urinary physiology Intracellular Homeostasis 0105 earth and related environmental sciences |
| Zdroj: | Molecular Neurobiology. 53:7078-7088 |
| ISSN: | 1559-1182 0893-7648 |
| Popis: | 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 ΔΨm 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, ΔΨm 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 ΔΨm 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. |
| Databáze: | OpenAIRE |
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