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DE-71-induced apoptosis involving intracellular calcium and the Bax-mitochondria-caspase protease pathway in human neuroblastoma cells In vitro
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China; Department of Biology and Chemistry, City University of Hong Kong, Kowloon, SAR, Hong Kong.
Graduate School of the Chinese Academy of Sciences, Beijing, China.
Graduate School of the Chinese Academy of Sciences, Beijing, China.ORCID iD: 0000-0001-6800-5658
Graduate School of the Chinese Academy of Sciences, Beijing, China.ORCID iD: 0000-0002-2134-3710
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2008 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 104, no 2, 341-351 p.Article in journal (Refereed) Published
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Abstract [en]

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 (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.

Place, publisher, year, edition, pages
Oxford University Press, 2008. Vol. 104, no 2, 341-351 p.
Keyword [en]
Apoptosis; Bax; Calcium; Caspase; Cytochrome c; Pentabrominated diphenyl ether (DE-71); SK-N-SH
National Category
Environmental Sciences
Research subject
Enviromental Science
Identifiers
URN: urn:nbn:se:oru:diva-50000DOI: 10.1093/toxsci/kfn088ISI: 000257789500011PubMedID: 18453545Scopus ID: 2-s2.0-47849094125OAI: oai:DiVA.org:oru-50000DiVA: diva2:950403
Available from: 2016-07-29 Created: 2016-04-28 Last updated: 2017-10-17Bibliographically approved

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