Neuronal Cell Degeneration Cascade

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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).