Dysregulation of calcium homeostasis and oxidative stress: interrelated mediators of tetrabromobisphenol a toxicity in primary cultures of rat cerebellar granule cells

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

Abstrakty

EN

There are alarming reports on cytotoxicity of the brominated flame retardant tetrabromobisphenol A (TBBPA) in the in vitro cellular models, that seem to be mediated by increases in the intracellular calcium concentration ([Ca2+] i) and oxidative stress. Still, the mechanisms of both these phenomena, their mutual cause‑and‑effect relationships and implication in the TBBPA-induced neuronal death are not clear. In our experiments the primary cultures of rat cerebellar granule cells (CGC) were acutely challenged with TBBPA. Such induced rises of [Ca2+]i appeared to result independently from the intracellular Ca2+ release via ryanodine receptors transformed into dysfunctional leak channels, and from Ca2+ influx mediated by NMDA receptors. These receptors seem to be activated indirectly, due to depolarization of neurons by TBBPA, which is mediated by the voltage-gated sodium channels and ionotropic glutamate receptors. TBBPA induced oxidative stress as evidenced by ROS production and decrease in GSH content and catalase activity. The pharmacological preventing of the TBBPA-induced rises in [Ca2+]i also entirely prevented oxidative stress induced by 10 µM TBBPA, while the effects of 25 µM TBBPA were only partially reduced. Application of free radical scavengers significantly reduced TBBPA‑induced oxidative stress, but did not interfere with rises in [Ca2+]i. This indicates that TBBPA-induced increase in [Ca2+]i is a primary and major event triggering oxidative stress, however at higher µM concentrations a Ca2+‑independent portion of oxidative stress emerges, and this effect seems to be directly induced by TBBPA. Furthermore, the separate application of inhibitors of TBBPA-induced Ca2+ transients and free radical scavengers, both provided a strong but incomplete cytoprotection, whereas combination of these substances completely prevented the death of neurons, showing that Ca2+ imbalance and oxidative stress are the triggers of acute TBBPA toxicity in CGC. FINANCIAL SUPPORT: This study was supported by the Polish National Science Centre grant no. 2012/05/B/ NZ7/03225.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.22

Twórcy

autor

Lazarewicz J.W.

• 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

Lenart J.

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

autor

Diamandakis D.

• 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