Goodman Y, Mattson M P
Sanders-Brown Research Center on Aging, University of Kentucky, Lexington 40536-0230, USA.
J Neurochem. 1996 Feb;66(2):869-72. doi: 10.1046/j.1471-4159.1996.66020869.x.
The transcription factor NF kappa B is activated by various signals associated with brain injury, including tumor necrosis factor (TNF), oxidative insults, and amyloid beta-peptide (A beta). We recently reported that TNFs activate NF kappa B in neurons and protect them against excitotoxic and oxidative insults, including A beta toxicity. We now report that C2-ceramide (C2), a membrane-permeant activator of NF kappa B, protects cultured rat hippocampal neurons against death induced by glutamate, FeSO4, and A beta. Protection was concentration dependent, specific (a ceramide analogue known not to activate NF kappa B was ineffective), required pretreatment, and was blocked by inhibitors of RNA and protein synthesis. Lipid peroxidation and accumulation of cellular peroxides induced by glutamate, FeSO4, and A beta were significantly attenuated in neurons pretreated with C2. The data indicate that C2 induces antioxidant pathways in neurons and suggest novel approaches for reducing neuronal injury in both acute and chronic neurodegenerative conditions.
转录因子核因子κB可被多种与脑损伤相关的信号激活，包括肿瘤坏死因子（TNF）、氧化损伤和β淀粉样肽（Aβ）。我们最近报道，TNF可激活神经元中的核因子κB，并保护它们免受兴奋毒性和氧化损伤，包括Aβ毒性。我们现在报道，C2-神经酰胺（C2），一种核因子κB的膜渗透性激活剂，可保护培养的大鼠海马神经元免受谷氨酸、硫酸亚铁和Aβ诱导的死亡。保护作用呈浓度依赖性、具有特异性（一种已知不激活核因子κB的神经酰胺类似物无效），需要预处理，并且被RNA和蛋白质合成抑制剂阻断。在用C2预处理的神经元中，谷氨酸、硫酸亚铁和Aβ诱导的脂质过氧化和细胞内过氧化物的积累显著减弱。数据表明，C2在神经元中诱导抗氧化途径，并为减少急性和慢性神经退行性疾病中的神经元损伤提出了新方法。
