TUMOR NECROSIS FACTORS PROTECT NEURONS AGAINST METABOLIC EXCITOTOXIC INSULTS AND PROMOTE MAINTENANCE OF CALCIUM HOMEOSTASIS
TUMOR NECROSIS FACTORS PROTECT NEURONS AGAINST METABOLIC EXCITOTOXIC INSULTS AND PROMOTE MAINTENANCE OF CALCIUM HOMEOSTASIS
复制标题
DOI：
10.1016/0896-6273(94)90159-7
复制
发表时间：
1994-01-01
期刊：
影响因子：
16.2
通讯作者：
MATTSON, MP
中科院分区：
文献类型：
--
作者：
CHENG, B;CHRISTAKOS, S;MATTSON, MP
新出现的数据表明，神经营养因子和细胞因子利用相似的信号转导机制。尽管神经营养因子可以保护中枢神经系统神经元免受各种损伤，但细胞因子在损伤反应中的作用尚不清楚。我们现在报道tnfβ和TNFalpha （1 - 100 ng/ml）可以保护培养的胚胎大鼠海马、间隔和皮质神经元免受葡萄糖剥夺引起的损伤和兴奋性氨基酸毒性。葡萄糖剥夺、谷氨酸、NMDA或AMPA诱导的细胞内钙浓度（[Ca2+]i）升高在经tnf - β预处理的神经元中减弱。tnf稳定[Ca2+]i的机制可能涉及调节参与维持[Ca2+]i稳态的蛋白质的表达，因为tnf β和TNfalpha都导致表达钙结合蛋白calbinin - d28k的神经元数量增加4- 8倍。这些数据表明，tnf在大脑对损伤的反应中具有神经保护作用。
Emerging data indicate that neurotrophic factors and cytokines utilize similar signal transduction mechanisms. Although neurotrophic factors can protect CNS neurons against a variety of insults, the role of cytokines in the injury response is unclear. We now report that TNFbeta and TNFalpha (1 - 100 ng/ml) can protect cultured embryonic rat hippocampal, septal, and cortical neurons against glucose deprivation-induced injury and excitatory amino acid toxicity. The elevation of intracellular calcium concentration ([Ca2+]i) induced by glucose deprivation, glutamate, NMDA, or AMPA was attenuated in neurons pretreated with TNFbeta. The mechanism whereby TNFs stabilize [Ca2+]i may involve regulation of the expression of proteins involved in maintaining [Ca2+]i homeostasis, since both TNFbeta and TNfalpha caused a 4- to 8-fold increase in the number of neurons expressing the calcium-binding protein calbindin-D28k. These data suggest a neuroprotective role for TNFs in the brain's response to injury.