Barker J E, Bolaños J P, Land J M, Clark J B, Heales S J
Department of Neurochemistry, Institute of Neurology, London, UK.
Dev Neurosci. 1996;18(5-6):391-6. doi: 10.1159/000111432.
In this study we have examined the susceptibility of the mitochondrial respiratory chain of astrocytes and astrocytes depleted of glutathione to peroxynitrite exposure. Astrocytes, as reported previously by us, appeared resistant to the actions of peroxynitrite. In contrast, depletion (-94%) of astrocytic glutathione rendered the cells susceptible with mitochondrial complexes I and II/III being decreased in activity by 80 and 64%, respectively, after peroxynitrite exposure. Furthermore, cell death, as judged by lactate dehydrogenase release, was significantly increased (+81%) in the glutathione-depleted astrocytes exposed to peroxynitrite. Glutathione depletion alone had no effect on any of the measured parameters. It is concluded that glutathione is an important intracellular defence against peroxynitrite and that when glutathione levels are compromised the mitochondrial respiratory chain is a vulnerable target and cell death ensues. In view of the relative paucity of neuronal glutathione, it is possible that astrocyte-derived peroxynitrite may, in certain pathological conditions, be released and diffuse into neighboring neurones where mitochondrial damage may occur.
在本研究中，我们检测了星形胶质细胞以及谷胱甘肽耗竭的星形胶质细胞的线粒体呼吸链对过氧亚硝酸盐暴露的敏感性。正如我们之前所报道的，星形胶质细胞对过氧亚硝酸盐的作用表现出抗性。相比之下，星形胶质细胞谷胱甘肽耗竭（-94%）使细胞变得敏感，过氧亚硝酸盐暴露后，线粒体复合物I和II/III的活性分别降低了80%和64%。此外，通过乳酸脱氢酶释放判断，在暴露于过氧亚硝酸盐的谷胱甘肽耗竭的星形胶质细胞中，细胞死亡显著增加（+81%）。单独的谷胱甘肽耗竭对任何测量参数均无影响。得出的结论是，谷胱甘肽是细胞内抵御过氧亚硝酸盐的重要防御物质，当谷胱甘肽水平受损时，线粒体呼吸链是一个易受攻击的靶点，随后会发生细胞死亡。鉴于神经元谷胱甘肽相对较少，在某些病理条件下，星形胶质细胞衍生的过氧亚硝酸盐可能会释放并扩散到邻近的神经元中，从而可能导致线粒体损伤。
