Altered expression of genes involved in programmed cell death in primary cultured rat cerebellar granule cells acutely challenged with tetrabromobisphenol A

摘要: In the present study, primary cultures of rat cerebellar granule cells (CGC) and RT2 Profiler PCR array were used to examine effect acutely applied brominated flame retardant tetrabromobisphenol A (TBBPA) on expression 84 genes related main modes programmed cell death. CGC, at 7th day culture, exposed 10 or 25μM TBBPA for 30min. Then, 3, 6, 24h later, viability was examined by staining with propidium iodide (PI) using calcein/ethidium homodimer (CA/ET) live/dead kit, RNA extracted evaluation gene RT-PCR. At 6 after treatment, number viable neurons decreased, according PI method, 75%, 58% 41%, respectively, CA/ET method 65%, 28%, respectively. CGC analyzed 3h treatment 6h 10μM TBBPA, only change in a reduction Tnf, which is associated autophagy may activate some pro-apoptotic proteins. Six hours 2 over-expressed, Tnfrsf10b Irgm, autophagy, that suppressed included anti-apoptotic Xiap, necrosis-related Commd4, Abl1, 5 involved (App, Atg3, Mapk8, Pten, Snca) participate two metabolic pathways: Atp6v1g2 (pro-apoptotic necrosis) Tnf (pro-apoptotic, autophagy). Autophagy-related Snca remained under-expressed accompanied over-expression Casp6, Birc3, (Htt Irgm) (Fas Tp53) are both apoptosis (pro-apoptotic) autophagy. These results show complex pattern TBBPA-evoked changes neuronal death, indicating no induction necrosis, an early suppression genes, followed delayed activation apoptosis.