Neuronal Cell Degeneration Cascade

PC 12细胞在神经生长因子（NGF）撤除后发生变性，仅当它们被NGF处理时，放线菌素D或虫草素阻断乳酸脱氢酶（LDH）活性的释放高达85-90%，剩余的释放是由于神经突变性。因此，NGF剥夺诱导的PC 12细胞的细胞死亡以转录依赖的方式发生，而血清剥夺诱导的PC 12细胞死亡已被报道是一个转录非依赖性的过程。高钾（> 35 mM）、CPT-cAMP（>0.1mM）、酸性和碱性FGF（10 ng/ml）的慢性去极化可完全阻止细胞死亡。在神经生长因子剥夺，快速脱磷酸化的主要酪氨酸磷酸化蛋白质，p120，p80，p70以及p140的trk发生随后逐渐下调激酶活性（丝氨酸/苏氨酸），这似乎需要RNA和蛋白质的合成。这些结果表明，由营养因子剥夺启动的去磷酸化级联反应是高度调节的，并可能构成程序性神经元死亡级联反应的一部分。

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).