Citation

Al-Mousa F, Michelangeli F. Chem. Biol. Interact. 2014; 207: 1-6.

Affiliation

School of Biosciences, University Of Birmingham, Edgbaston, Birmingham, UK, B15 2TT.

Copyright

(Copyright © 2014, Elsevier Publishing)

DOI

10.1016/j.cbi.2013.10.021

PMID

24189551

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 6 other unrelated BFRs, were assessed in SH-SY5Y human neuroblastoma cells by 24 hour 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.

Language: en