Casaccia-Bonnefil P, Carter B D, Dobrowsky R T, Chao M V
Department of Cell Biology and Anatomy, Hematology/Oncology Division, Cornell University Medical College, New York 10021, USA.
Nature. 1996 Oct 24;383(6602):716-9. doi: 10.1038/383716a0.
Members of the nerve growth factor (NGF) family promote the survival of neurons during development. NGF specifically activates the receptor trkA, initiating a signal transduction cascade which ultimately blocks cell death. Here we show that NGF can have the opposite effect, inducing the death of mature oligodendrocytes cultured from postnatal rat cerebral cortex. This effect was highly specific, because NGF had no effect on oligodendrocyte precursors and astrocytes. Other neurotrophins such as brain-derived neurotrophin factor (BDNF) and neurotrophin-3 (NT-3) did not induce cell death. NGF binding to mature oligodendrocytes expressing the p75 neurotrophin receptor, but not trkA, resulted in a sustained increase of intracellular ceramide and c-Jun amino-terminal kinase (JNK) activity, which are thought to participate in a signal transduction pathway leading to cell death. Taken together, these results indicate that NGF has the ability to promote cell death in specific cell types through a ligand-dependent signalling mechanism involving the p75 neurotrophin receptor.
神经生长因子（NGF）家族成员在发育过程中促进神经元存活。NGF特异性激活受体trkA，启动信号转导级联反应，最终阻止细胞死亡。在此我们表明，NGF可产生相反的作用，诱导出生后大鼠大脑皮层培养的成熟少突胶质细胞死亡。这种作用具有高度特异性，因为NGF对少突胶质细胞前体和星形胶质细胞没有影响。其他神经营养因子，如脑源性神经营养因子（BDNF）和神经营养因子-3（NT-3），不会诱导细胞死亡。NGF与表达p75神经营养因子受体而非trkA的成熟少突胶质细胞结合，导致细胞内神经酰胺和c-Jun氨基末端激酶（JNK）活性持续增加，这些被认为参与导致细胞死亡的信号转导途径。综上所述，这些结果表明，NGF能够通过涉及p75神经营养因子受体的配体依赖性信号传导机制促进特定细胞类型的细胞死亡。
