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2011 | 71 | S |
Tytuł artykułu

Common mechanisms of interacellular calcium release by TBBPA and thapsigargin in cultured neurons

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Języki publikacji
Tetrabromobisphenol A (TBBPA) is a brominated flame retardant and the environmental toxin affecting the brain. The molecular mechanisms of the TBBPA-induced neurotoxicity are still unclear although recent studies suggest a role of calcium imbalance. It has been hypothesized that TBBPA may act as an intracellular calcium releaser from the stores in endoplasmic reticulum. To verify this hypothesis in the present study we examined changes in the intracellular calcium homeostasis induced by TBBPA, and their pharmacological modulation. Experiments were performed using an in vitro model of the primary cultures of rat cerebellar granule cells at 7th day in vitro. To evaluate TBBPA neurotoxicity, the cells were exposed for 30 min to TBBPA, and neuronal viability was tested after 24 h with propidium iodide staining. Changes in calcium homeostasis were characterized using the calcium-sensitive fluorescent probe fluo-3. The results demonstrated that TPPBA in concentrations exceeding 5 µM triggered rise in the intracellular calcium level, which was sensitive to inhibitors of ryanodine receptors 2.5 µM bastadin 10 with 200 µM ryanodine, but not to 2ABP, which inhibits IP3 receptors. The same features were disclosed for the effects of thapsigargin, that is a recognized inhibitor of the calcium pump SERCA and a well known calcium releaser. TPPBA in the concentration-dependent manner in the range of 2.5 - 100 µM induced severe neurotoxicity. The toxic effect of TPPBA in concentrations up to 10 - 15 µM was insensitive to antagonists of ryanodine receptors, bastadin 10 with ryanodine. Collectively, these results indicate that TBBP-A like thapsigargin is a calcium releaser destabilizing the ryanodine receptors, however this effect does not explain the mechanism of TBBPA neurotoxicity. This work was supported by the MNiSW grant N N401 024635.
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Opis fizyczny
  • Department of Neurochemistry, Mossakowski Medical Research Center PAS, Warsaw, Poland
  • Department of Neurochemistry, Mossakowski Medical Research Center PAS, Warsaw, Poland
  • Department of Neurochemistry, Mossakowski Medical Research Center PAS, Warsaw, Poland
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