The widely utilized brominated flame retardant tetrabromobisphenol A (TBBPA) is a potent inhibitor of the SERCA Ca2+ pump

Oluseye Ogunbayo, Francesco Michelangeli

Research output: Contribution to journalArticle

40 Citations (Scopus)


TBBPA (tetrabromobisphenol A) is currently the most widely used type of BFR (brominated flame retardant) 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 animal and humans. BFRs including TBBPA have also been shown to be cytotoxic and potentially endocrine-disrupting to a variety of cells in culture. Furthermore, TBBPA has specifically been shown to cause disruption of Ca2+ homoeostasis within cells, which may be the underlying cause of its cytotoxicity. In this study, we have demonstrated that TBBPA is a potent non-isoform-specific inhibitor of the SERCA (sarcoplasmic/endoplasmic reticulum Ca2+-ATPase) (apparent K-i 0.46-2.3 mu M), thus we propose that TBBPA inhibition of SERCA contributes in some degree to Ca2+ signalling disruption. TBBPA binds directly to the SERCA without the need to partition into the phospholipid bilayer. From activity results and Ca2+-induced conformational results, it appears that the major effect of TBBPA is to decrease the SERCA affinity for Ca2+ (increasing the K-d from approx. 1 mu M to 30 AM in the presence of 10 AM TBBPA). Low concentrations of TBBPA can quench the tryptophan fluorescence of the SERCA and this quenching can be reversed by BHQ [2,5-di-(t-butyl)-1,4-hydroquinone] and 4-n-nonylphenol, but not thapsigargin, indicating that TBBPA and BHQ may be binding to similar regions in the SERCA.
Original languageEnglish
Pages (from-to)407-415
Number of pages9
JournalBiochemical Journal
Issue number3
Early online date5 Sept 2007
Publication statusPublished - 15 Dec 2007


  • sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)
  • brominated flame retardant
  • calcium signalling
  • tetrabromobisphenol A
  • affinity
  • E1 and E2 conformation


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