The widely utilized brominated flame retardant, tetrabromobisphenol a (TBBPA) is a potent inhibitor of the SERCA Ca 2+} pump

Oluseye A Ogunbayo , Francesco Michelangeli (1)

1 School of Biosciences

Tetrabromobisphenol A (TBBPA) is currently the most widely used type of brominated flame retardant (BFR), employed to reduce the combustibility of a large variety of electronic and other manufactured products. Recent studies have indicated that BFRs, including TBBPA, are bio-accumulating within humans at relatively high concentrations. BFRs, including TBBPA have also been shown to be cytotoxic and potentially endocrine disrupting in a variety of cell types. Furthermore, TBBPA has specifically been shown to cause disruption of Ca 2+} homeostasis within cells, which may be the underlying cause of its toxicity. In this study, we have demonstrated that TBBPA is a potent non-isoform specific inhibitor of the SERCA Ca 2+}-ATPase (apparent Ki 0.46 - 2.3µM), thus, we propose that TBBPA inhibition of Ca 2+} ATPase contributes, at least in part, to Ca 2+} signalling disruption. TBBPA binds directly to the ATPase without the need to partition into the phospholipid bilayer. From activity data and Ca 2+}-induced conformational data, it appears that the major effect of TBBPA is to decrease the Ca 2+} ATPase affinity for Ca 2+} binding (increasing the K d} from approx. 1µM to 30µM in the presence of 10µM TBBPA). Low concentrations of TBBPA can quench the tryptophan fluorescence of the ATPase and this quenching can be reversed by 2,5-di-tert-butylhydroquinone (BHQ) and 4-n-nonylphenol, but not thapsigargin, indicating that TBBPA and BHQ may be binding to similar regions in the Ca 2+}-ATPase.

Mots clés: Life Sciences

Oluseye A Ogunbayo, Francesco Michelangeli. The widely utilized brominated flame retardant, tetrabromobisphenol a (TBBPA) is a potent inhibitor of the SERCA Ca 2+} pump. Biochemical Journal, 2007, 408 (3), pp.407-415. ⟨10.1042/BJ20070843⟩. ⟨hal-00478836⟩