Neuronal Cell Degeneration Cascade

PC12细胞在停用神经生长因子(NGF)后才发生变性，只有在NGF、放线菌素D或虫草素阻断乳酸脱氢酶(LDH)活性的85-90%的情况下，残留的LDH的释放是由于轴突变性所致。因此，NGF剥夺诱导的PC12细胞死亡是以转录依赖的方式发生的，而血清剥夺诱导的PC12细胞死亡被报道是一个转录不依赖的过程。高钾(&gt；35 mM)、CPT-cAMP(&gt；0.1 mM)、酸性和碱性成纤维细胞生长因子(10 ng/ml)的慢性去极化可完全阻止细胞死亡。在缺乏NGF的情况下，主要的酪氨酸磷酸化蛋白p120、p80、p70和p140trk迅速去磷酸化，随后激酶活性(Ser/Thr)逐渐下调，这似乎需要RNA和蛋白质的合成。这些结果表明，营养因子剥夺所启动的去磷酸级联反应被高度抑制，可能构成了神经元程序性死亡级联反应的一部分(S)。

PC12 cells undergo degeneration after nerve growth factor (NGF) withdrawal only when they have been treated with NGF Actinomycin D or cordycepin blocked the release of lactate dehyrogenase (LDH) activity up to 85-90%; the residual release was due to neurite degeneration. Thus, NGF deprivation-induced cell death of PC12 cells occurs in a transcription-dependent manner, while serum deprivation-induced PC12 cell death has been reported to be a transcription-independent process. The cell death was completely prevented by chronic depolarization with high potassium (>35mM), CPT-cAMP(>0.1mM), acidic and basic FGF(10ng/ml). Upon NGF deprivation, rapid dephosphorylation of major tyrosine-phosphorylated proteins, p120, p80, p70 as well as p140 trk occurred followed by gradual down-regulation of kinase activities (Ser/Thr) which appears to require RNA and protein synthesis. These results suggest that a dephosphorylation cascade initiated by trophic factor deprivation is highly reulated, and may constitute a part of programmed neuronal death cascade(s).