Behrens M M, Martínez J L, Moratilla C, Renart J
Institute of Biomedical Investigations, Cosejo Superior de Investigaciones Científicas, CSIC, Department of Biochemistry, Universidad Autónoma de Madrid, Spain.
Cell Growth Differ. 1995 Nov;6(11):1375-80.
The protein kinase C inhibitor bisindolylmaleimide GF109203X has a dual effect on the behavior of the neuroblastoma cell line Neuro-2A; when the inhibitor is added in conditions that induce differentiation (absence of serum), neurite outgrowth is potentiated in a dose-dependent manner. However, if the inhibitor is added in growth-promoting conditions (presence of serum), programmed cell death (apoptosis) is induced, as assessed by internucleosomal DNA cleavage and specific immunoassays. This effect is also seen with other specific protein kinase C inhibitors. Bcl2 gene overexpression protects Neuro-2A cells from apoptosis, as has been found in other systems. We also show that calpain I, a neutral Ca(2+)-activated proteinase, participates in this apoptotic pathway. Our results point to a key role of protein kinase C in the regulation of growth and differentiation in Neuro-2A cells.
蛋白激酶C抑制剂双吲哚马来酰胺GF109203X对神经母细胞瘤细胞系Neuro-2A的行为有双重作用；当在诱导分化的条件下（无血清）添加该抑制剂时，神经突生长以剂量依赖的方式增强。然而，如果在促进生长的条件下（有血清）添加该抑制剂，则会诱导程序性细胞死亡（凋亡），这通过核小体间DNA裂解和特异性免疫测定来评估。其他特异性蛋白激酶C抑制剂也有此作用。如在其他系统中所发现的那样，Bcl2基因的过表达可保护Neuro-2A细胞免于凋亡。我们还表明，钙蛋白酶I，一种中性Ca(2+)激活的蛋白酶，参与了这条凋亡途径。我们的结果表明蛋白激酶C在Neuro-2A细胞生长和分化的调节中起关键作用。
