Neuroprotective effects of α-tocopherol on oxidative stress in rat striatal cultures
Neuroprotective effects of α-tocopherol on oxidative stress in rat striatal cultures
复制标题
DOI：
10.1016/s0014-2999(03)01495-x
复制
发表时间：
2003-03
影响因子：
5
通讯作者：
Fumitaka Osakada;A. Hashino;T. Kume;H. Katsuki;S. Kaneko;A. Akaike
中科院分区：
文献类型：
--
作者：
Fumitaka Osakada;A. Hashino;T. Kume;H. Katsuki;S. Kaneko;A. Akaike
自由基增加引起的氧化应激在神经元死亡中起着重要作用。我们使用大鼠纹状体神经元的原代培养物研究了 α-生育酚对氧化应激诱导的细胞毒性的影响。浓度为 1–10 μM 的 α-生育酚可显着防止超氧自由基 (O2−) 供体 1,1'-二甲基-4,4'-二氯化联吡啶（百草枯）诱导的细胞毒性。相比之下，α-生育酚不影响过氧化氢（H2O2）的细胞毒性，过氧化氢通过金属催化的芬顿反应增强羟基自由基（·OH）的形成。 α-生育酚显着抑制一氧化氮 (NO) 供体、S-亚硝基半胱氨酸和 3-吗啉代亚胺 (SIN-1) 的细胞毒性。 α-生育酚对 L-丁硫氨酸-[S,R]-亚磺酰亚胺 (BSO) 诱导的细胞毒性表现出有效的保护作用，这种细胞毒性会导致细胞内谷胱甘肽的消耗。此外，α-生育酚对非特异性蛋白激酶抑制剂星形孢菌素诱导的细胞毒性具有中等但显着的抑制作用，已知星形孢菌素可诱导包括神经元在内的许多类型细胞的凋亡。这些结果表明，α-生育酚通过减少氧化应激来保护纹状体神经元，可能是通过降低细胞内 O2 水平，并且至少部分是通过抑制细胞凋亡。
Oxidative stress caused by an increase in free radicals plays an important role in neuronal death. We investigated the effects of α-tocopherol on oxidative stress-induced cytotoxicity using primary cultures of rat striatal neurons. α-Tocopherol at concentrations of 1–10 μM significantly prevented cytotoxicity induced by superoxide radical (O2−) donor, 1,1′-dimethyl-4,4′-bipyridium dichloride (paraquat). In contrast, α-tocopherol did not affect the cytotoxicity of hydrogen peroxide (H2O2), which enhances hydroxyl radical (·OH) formation by metal-catalyzed Fenton reactions. α-Tocopherol significantly inhibited the cytotoxicity of nitric oxide (NO) donors, S-nitrosocysteine and 3-morpholinosydnonimine (SIN-1). α-Tocopherol showed potent protection against cytotoxicity induced by l-buthionine-[S,R]-sulfoximine (BSO), which causes depletion of intracellular glutathione. Moreover, α-tocopherol afforded a moderate but significant inhibition of cytotoxicity induced by a non-specific protein kinase inhibitor, staurosporine, which is known to induce apoptosis in many types of cells including neurons. These results suggest that α-tocopherol protects striatal neurons by the reduction of oxidative stress, presumably by decreasing intracellular O2−levels, and at least partly by the inhibition of apoptosis.