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Article: DE-71-induced apoptosis involving intracellular calcium and the bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitro

TitleDE-71-induced apoptosis involving intracellular calcium and the bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitro
Authors
Issue Date2008
PublisherOxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/
Citation
Toxicological Sciences, 2008, v. 104 n. 2, p. 341-351 How to Cite?
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 (3μM) 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. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/179065
ISSN
2015 Impact Factor: 3.88
2015 SCImago Journal Rankings: 1.686
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYu, Ken_US
dc.contributor.authorHe, Yen_US
dc.contributor.authorYeung, LWYen_US
dc.contributor.authorLam, PKSen_US
dc.contributor.authorWu, RSSen_US
dc.contributor.authorZhou, Ben_US
dc.date.accessioned2012-12-19T09:51:44Z-
dc.date.available2012-12-19T09:51:44Z-
dc.date.issued2008en_US
dc.identifier.citationToxicological Sciences, 2008, v. 104 n. 2, p. 341-351en_US
dc.identifier.issn1096-6080en_US
dc.identifier.urihttp://hdl.handle.net/10722/179065-
dc.description.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 (3μM) 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. © The Author 2008. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://toxsci.oxfordjournals.org/en_US
dc.relation.ispartofToxicological Sciencesen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCalcium - Metabolismen_US
dc.subject.meshCaspases - Biosynthesisen_US
dc.subject.meshCell Line, Tumor - Drug Effectsen_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshCytochromes C - Metabolismen_US
dc.subject.meshDna Damageen_US
dc.subject.meshDna, Neoplasm - Drug Effectsen_US
dc.subject.meshDizocilpine Maleate - Pharmacologyen_US
dc.subject.meshDose-Response Relationship, Drugen_US
dc.subject.meshEnzyme Inductionen_US
dc.subject.meshFlame Retardants - Toxicityen_US
dc.subject.meshHalogenated Diphenyl Ethersen_US
dc.subject.meshHumansen_US
dc.subject.meshMitochondria - Drug Effects - Metabolismen_US
dc.subject.meshNeuroblastoma - Drug Therapy - Metabolismen_US
dc.subject.meshPhenyl Ethers - Toxicityen_US
dc.subject.meshPolybrominated Biphenyls - Toxicityen_US
dc.subject.meshReactive Oxygen Species - Metabolismen_US
dc.subject.meshBcl-2-Associated X Protein - Metabolismen_US
dc.titleDE-71-induced apoptosis involving intracellular calcium and the bax-mitochondria-caspase protease pathway in human neuroblastoma cells in vitroen_US
dc.typeArticleen_US
dc.identifier.emailWu, RSS: rudolfwu@hku.hken_US
dc.identifier.authorityWu, RSS=rp01398en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1093/toxsci/kfn088en_US
dc.identifier.pmid18453545-
dc.identifier.scopuseid_2-s2.0-47849094125en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47849094125&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume104en_US
dc.identifier.issue2en_US
dc.identifier.spage341en_US
dc.identifier.epage351en_US
dc.identifier.isiWOS:000257789500011-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridYu, K=35757266000en_US
dc.identifier.scopusauthoridHe, Y=16241582000en_US
dc.identifier.scopusauthoridYeung, LWY=9735175200en_US
dc.identifier.scopusauthoridLam, PKS=7202365776en_US
dc.identifier.scopusauthoridWu, RSS=7402945079en_US
dc.identifier.scopusauthoridZhou, B=7401906781en_US

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