RESUMO
@#【Abstract】 【Objective】To investigate the mechanisms implicated in ataxia telangiectasia mutated(ATM)inhibitioncaused apoptosis in the cultured cerebellar granule neurons.【Methods】Primary cerebellar granule neurons(CGN)isolated from neonatal Sprague Dawley rats of 7-8 days were divided into the following groups:25 K group(survival group),5 K group(apoptosis group)and 25 K + KU-55933 treatment group(ATM inhibition group),25 K + KU-55933 + Mithramycin A treatment group(MMA group),25 K + KU-55933 + Chromonycin A3 treatment group(CMA3 group). The protein expression of p-ATM,ATM,Bim and Caspase 3 were detected by Western Blot. The apoptotic cells with nuclear pyknosis were detected by Hoechst-staining.【Results】Compared with 25 K group,the result of western blot showed that the protein expression of Bim and Caspase 3 were increased in the ATM inhibition group(P < 0.05). Compared with 25 K group,the nuclear pyknosis rate of 5 K group and ATM inhibition group were significantly increased(P < 0.05). Inhibition of Bim by Mithramycin A or Chromomycin A3 remarkably reversed ATM inhibition-caused apoptosis.【Conclusion】Inhibition of ATM induce Bim dependent apoptosis in cultured cerebellar granule neurons.