Tetrabromobisphenol A directly interferes with activity of NMDA isolated cortical membranes

• Autorzy: Diamandakis D. , Zieminska E. , Salinska E. , Lazarewicz J.W.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: The results of early studies suggested a role of glutamate receptors in the mechanism of increases in intracellular Ca2+ concentration ([Ca2+]i ) and cytotoxicity induced by the brominated flame retardant, tetrabromobisphenol-A (TBBPA). Although now interest has focused mainly on TBBPA-induced Ca2+ release from intracellular stores, here we revisited the former issue and tested the involvement of NMDA receptors (NMDARs) in Ca2+ imbalance in neurons induced by TBBPA. METHODS: These effects were examined in primary cultures of rat cerebellar granule cells (CGC), and then, using isolated cortical membranes we checked whether TBBPA directly interacts with the agonist and modulatory sites of the NMDAR complex. On the 7th day in vitro CGC were treated with TBBPA at low µM concentrations. 45Ca uptake was detected and changes in [Ca2+]i , and plasma membrane potential were measured using fluorescent probes fluo-3 and oxonol VI, respectively. Moreover effects of TBBPA on specific binding of [3 H]MK-801, [3 H]glutamate and [3 H]glycine to isolated fraction of the rat brain cortex membranes were studied. RESULTS: The results demonstrated that TBBPA concentrationdependently increased 45Ca uptake and [Ca2+]i in CGC, and the increase was partially inhibited by NMDARs antagonist, MK-801. This effect was additive to glutamate-induced Ca2+ transients. TBBPA increased oxonol VI fluorescence in CGC reflecting depolarization of the cultured neurons. The binding assays demonstrated potentiation by TBBPA binding of [ 3 H]MK-801 in the presence of NMDA and glycine, with maximum at 20 µM TBBPA, which was inhibited by spermidine and antagonists of the polyamines’ site; inhibition by TBBPA of [ 3 H]glutamate binding, and no significant effect on [3 H]glycine binding. CONCLUSIONS: TBBPA directly enhances the activity of NMDARs in neuronal membranes by interfering with their modulatory sites, and by inducing depolarization of neurons. Supported by the NCN grant 2012/05/B/NZ7/03225

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S39

Twórcy

autor

Diamandakis D.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Zieminska E.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Salinska E.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Lazarewicz J.W.

• Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland