Gunn-Moore F J, Tavaré J M
Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
Neurosci Lett. 1998 Jun 26;250(1):53-6. doi: 10.1016/s0304-3940(98)00438-8.
It has been reported that in differentiated PC12 cells and neurons from the superior cervical ganglion and hippocampus, that the activation of the stress-activated protein kinases jun-N-terminal kinase (JNK) and/or p38 mitogen-activated protein (p38MAP) kinase is central to the induction of apoptosis by serum or neurotrophic factor withdrawal. Here we demonstrate that in cerebellar granule cells, withdrawal of serum does not result in the activation of JNK or p38MAP kinase, under conditions where profound apoptosis was observed. In addition, these protein kinases were not activated during the induction of apoptosis caused by addition of excitotoxic levels of glutamate or of beta-amyloid (25-35) peptide. BDNF and insulin can prevent apoptosis induced by serum withdrawal or the addition of glutamate or beta-amyloid peptide. EGF on the other can prevent apoptosis induced by glutamate and beta-amyloid peptide, but not that caused by serum withdrawal. We conclude that the induction of apoptosis of cerebellar granule cells is independent of JNK or p38MAP kinase activation and that the mechanism by which serum withdrawal promotes apoptosis of these neurons may differ from that caused by glutamate and beta-amyloid peptide.
据报道，在分化的PC12细胞以及来自颈上神经节和海马体的神经元中，应激激活蛋白激酶c-Jun氨基末端激酶（JNK）和/或p38丝裂原活化蛋白（p38MAP）激酶的激活是血清或神经营养因子撤除诱导细胞凋亡的核心。在此我们证明，在小脑颗粒细胞中，在观察到严重细胞凋亡的条件下，血清撤除不会导致JNK或p38MAP激酶的激活。此外，在由添加兴奋性毒性水平的谷氨酸或β-淀粉样蛋白（25-35）肽诱导细胞凋亡的过程中，这些蛋白激酶也未被激活。脑源性神经营养因子（BDNF）和胰岛素可以预防血清撤除或添加谷氨酸或β-淀粉样蛋白肽所诱导的细胞凋亡。另一方面，表皮生长因子（EGF）可以预防由谷氨酸和β-淀粉样蛋白肽诱导的细胞凋亡，但不能预防血清撤除所导致的细胞凋亡。我们得出结论，小脑颗粒细胞凋亡的诱导独立于JNK或p38MAP激酶的激活，并且血清撤除促进这些神经元凋亡的机制可能不同于由谷氨酸和β-淀粉样蛋白肽所导致的机制。
