The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD).

Hdl Handle:
http://hdl.handle.net/10034/609045
Title:
The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD).
Authors:
Al-Mousa, Fawaz; Michelangeli, Francesco
Abstract:
Hexabromocyclododecane (HBCD) is a widely utilised brominated flame retardant (BFR). It has been shown to bio-accumulate within organisms, including man, and possibly cause neurological disorders. The acute neurotoxicity of HBCD, and six other unrelated BFRs, were assessed in SH-SY5Y human neuroblastoma cells by 24h viability assays and HBCD proved to be the most lethal (LC50, 3μM). In addition, the effects of these BFRs were also assessed for their potency at inhibiting the sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) derived from the SH-SY5Y cells and again HBCD was the most potent (IC50, 2.7μM). The data for the other BFRs tested showed a direct correlation (coefficient 0.94) between the potencies of inducing cell death and inhibiting the Ca(2+) ATPase, indicating that SERCA is likely to be the molecular target for acute toxicity. Mechanistic studies of HBCD on the Ca(2+) ATPase suggest that it affects ATP binding, phosphorylation as well as the E2 to E1 transition step.
Affiliation:
University of Birmingham, UK
Citation:
Al-Mousa, F., Michelangeli, F. (2014). The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD). Chemico-Biological Interactions, 207, 1-6. http://dx.doi.org/10.1016/j.cbi.2013.10.021.
Publisher:
Elsevier
Journal:
Chemico-Biological Interactions
Publication Date:
1-Jan-2014
URI:
http://hdl.handle.net/10034/609045
DOI:
10.1016/j.cbi.2013.10.021
Additional Links:
http://www.sciencedirect.com/science/article/pii/S0009279713002755
Type:
Article
Language:
en
ISSN:
0009-2797
Appears in Collections:
Biological Sciences

Full metadata record

DC FieldValue Language
dc.contributor.authorAl-Mousa, Fawazen
dc.contributor.authorMichelangeli, Francescoen
dc.date.accessioned2016-05-11T11:20:48Zen
dc.date.available2016-05-11T11:20:48Zen
dc.date.issued2014-01-01en
dc.identifier.citationAl-Mousa, F., Michelangeli, F. (2014). The sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD). Chemico-Biological Interactions, 207, 1-6. http://dx.doi.org/10.1016/j.cbi.2013.10.021.en
dc.identifier.issn0009-2797en
dc.identifier.doi10.1016/j.cbi.2013.10.021en
dc.identifier.urihttp://hdl.handle.net/10034/609045en
dc.description.abstractHexabromocyclododecane (HBCD) is a widely utilised brominated flame retardant (BFR). It has been shown to bio-accumulate within organisms, including man, and possibly cause neurological disorders. The acute neurotoxicity of HBCD, and six other unrelated BFRs, were assessed in SH-SY5Y human neuroblastoma cells by 24h viability assays and HBCD proved to be the most lethal (LC50, 3μM). In addition, the effects of these BFRs were also assessed for their potency at inhibiting the sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) derived from the SH-SY5Y cells and again HBCD was the most potent (IC50, 2.7μM). The data for the other BFRs tested showed a direct correlation (coefficient 0.94) between the potencies of inducing cell death and inhibiting the Ca(2+) ATPase, indicating that SERCA is likely to be the molecular target for acute toxicity. Mechanistic studies of HBCD on the Ca(2+) ATPase suggest that it affects ATP binding, phosphorylation as well as the E2 to E1 transition step.en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urlhttp://www.sciencedirect.com/science/article/pii/S0009279713002755en
dc.subjectbiochemistryen
dc.subjecttoxicologyen
dc.titleThe sarcoplasmic-endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the likely molecular target for the acute toxicity of the brominated flame retardant hexabromocyclododecane (HBCD).en
dc.typeArticleen
dc.contributor.departmentUniversity of Birmingham, UKen
dc.identifier.journalChemico-Biological Interactionsen
dc.date.accepted2013-10-23en
or.grant.openaccessYesen
rioxxterms.funderunfundeden
rioxxterms.identifier.projectunfunded researchen
rioxxterms.versionAMen
rioxxterms.licenseref.startdate2016-05-11en
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