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DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro
Yu, Ke1,2; He, Yuhe3; Yeung, Leo W. Y.3; Lam, Paul K. S.3; Wu, Rudolf S. S.3; Zhou, Bingsheng1; Zhou, BS, Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China
2008-08-01
Source PublicationTOXICOLOGICAL SCIENCES
ISSN1096-6080
Volume104Issue:2Pages:341-351
AbstractPolybrominated diphenyl ethers (PBDEs) are used extensively as flame-retardants and are ubiquitous in the environment and in wildlife and human tissue. Recent studies have shown that PBDEs induce neurotoxic effects in vivo and apoptosis in vitro. However, the signaling mechanisms responsible for these events are still unclear. In this study, we investigated the action of a commercial mixture of PBDEs (pentabrominated diphenyl ether, DE-71) on a human neuroblastoma cell line, SK-N-SH. A cell viability test showed a dose-dependent increase in lactate dehydrogenase leakage and 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction. Cell apoptosis was observed through morphological examination, and DNA degradation in the cell cycle and cell apoptosis were demonstrated using flow cytometry and DNA laddering. The formation of reactive oxygen species was not observed, but DE-71 was found to significantly induce caspase-3, -8, and -9 activity, which suggests that apoptosis is not induced by oxidative stress but via a caspase-dependent pathway. We further investigated the intracellular calcium ([Ca2+](i)) levels using flow cytometry and observed an increase in the intracellular Ca2+ concentration with a time-dependent trend. We also found that the N-methyl d-aspartate (NMDA) receptor antagonist MK801 (3 mu M) significantly reduced DE-71-induced cell apoptosis. The results of a Western blotting test demonstrated that DE-71 treatment increases the level of Bax translocation to the mitochondria in a dose-dependent fashion and stimulates the release of cytochrome c (Cyt c) from the mitochondria into the cytoplasm. Overall, our results indicate that DE-71 induces the apoptosis of ([Ca2+](i)) in SK-N-SH cells via Bax insertion, Cyt c release in the mitochondria, and the caspase activation pathway.; Polybrominated diphenyl ethers (PBDEs) are used extensively as flame-retardants and are ubiquitous in the environment and in wildlife and human tissue. Recent studies have shown that PBDEs induce neurotoxic effects in vivo and apoptosis in vitro. However, the signaling mechanisms responsible for these events are still unclear. In this study, we investigated the action of a commercial mixture of PBDEs (pentabrominated diphenyl ether, DE-71) on a human neuroblastoma cell line, SK-N-SH. A cell viability test showed a dose-dependent increase in lactate dehydrogenase leakage and 3-(4,5-dimethylthia-zol-2-yl)-2,5-diphenyl-tetrazolium bromide reduction. Cell apoptosis was observed through morphological examination, and DNA degradation in the cell cycle and cell apoptosis were demonstrated using flow cytometry and DNA laddering. The formation of reactive oxygen species was not observed, but DE-71 was found to significantly induce caspase-3, -8, and -9 activity, which suggests that apoptosis is not induced by oxidative stress but via a caspase-dependent pathway. We further investigated the intracellular calcium ([Ca2+](i)) levels using flow cytometry and observed an increase in the intracellular Ca2+ concentration with a time-dependent trend. We also found that the N-methyl d-aspartate (NMDA) receptor antagonist MK801 (3 mu M) significantly reduced DE-71-induced cell apoptosis. The results of a Western blotting test demonstrated that DE-71 treatment increases the level of Bax translocation to the mitochondria in a dose-dependent fashion and stimulates the release of cytochrome c (Cyt c) from the mitochondria into the cytoplasm. Overall, our results indicate that DE-71 induces the apoptosis of ([Ca2+](i)) in SK-N-SH cells via Bax insertion, Cyt c release in the mitochondria, and the caspase activation pathway.
SubtypeArticle
KeywordPentabrominated Diphenyl Ether (De-71) Apoptosis Bax Caspase Calcium Cytochrome c Sk-n-sh
Department[Yu, Ke; Zhou, Bingsheng] Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China; [Yu, Ke] Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China; [He, Yuhe; Yeung, Leo W. Y.; Lam, Paul K. S.; Wu, Rudolf S. S.] City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China
Subject AreaToxicology
DOI10.1093/toxsci/kfn088
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Indexed BySCI
Language英语
WOS Research AreaToxicology
WOS SubjectToxicology
WOS IDWOS:000257789500011
WOS KeywordPOLYBROMINATED DIPHENYL ETHERS ; BROMINATED FLAME RETARDANTS ; CEREBELLAR GRANULE CELLS ; POLYCHLORINATED BIPHENYL MIXTURES ; SK-N-SH ; NEONATAL EXPOSURE ; SPONTANEOUS BEHAVIOR ; TEMPORAL TRENDS ; ADULT MICE ; MOTHERS MILK
Citation statistics
Cited Times:40[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/152342/8056
Collection期刊论文
Corresponding AuthorZhou, BS, Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China
Affiliation1.Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China
3.City Univ Hong Kong, Dept Biol & Chem, Kowloon, Hong Kong, Peoples R China
Recommended Citation
GB/T 7714
Yu, Ke,He, Yuhe,Yeung, Leo W. Y.,et al. DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro[J]. TOXICOLOGICAL SCIENCES,2008,104(2):341-351.
APA Yu, Ke.,He, Yuhe.,Yeung, Leo W. Y..,Lam, Paul K. S..,Wu, Rudolf S. S..,...&Zhou, BS, Chinese Acad Sci, State Key Lab Freshwater Ecol & Biotechnol, Inst Hydrobiol, Wuhan 430072, Peoples R China.(2008).DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro.TOXICOLOGICAL SCIENCES,104(2),341-351.
MLA Yu, Ke,et al."DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro".TOXICOLOGICAL SCIENCES 104.2(2008):341-351.
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