Röhrdanz E, Schmuck G, Ohler S, Tran-Thi Q H, Kahl R
Institut für Toxikologie, Heinrich-Heine-Universität Düsseldorf, Germany.
Arch Toxicol. 2001 May;75(3):150-8. doi: 10.1007/s002040000206.
Oxidative stress has been causally linked to a variety of neurodegenerative diseases. To clarify the role of the antioxidant enzyme (AOE) system in oxidative brain damage primary cultures of rat astroglial cells were exposed to hydrogen peroxide (H2O2). Expression of AOEs and several parameters for cell viability and functionality were measured. In our experiments astrocytes responded to low concentrations of H2O2 exposure with a pronounced generation of ROS which ran parallel with induction of lipid peroxidation. This distinct oxidative stress was not reflected in cell viability or functionality parameters measured. Cytotoxicity, a decrease in glutathione content of astrocytes, and impairment of mitochondrial functions became obvious only for higher concentrations of H2O2. After H2O2 exposure catalase, manganese superoxide dismutase, and glutathione peroxidase expression levels were found to be increased, whereas copper/zinc superoxide dismutase mRNA expression was not affected. These data indicate that the AOE system of astrocytes can be directly regulated by oxidative stress and may thus contribute to protection of cells against oxidative insults.
氧化应激与多种神经退行性疾病存在因果关联。为阐明抗氧化酶(AOE)系统在氧化性脑损伤中的作用,将大鼠星形胶质细胞的原代培养物暴露于过氧化氢(H2O2)中。检测了AOE的表达以及细胞活力和功能的几个参数。在我们的实验中,星形胶质细胞对低浓度H2O2暴露的反应是产生大量活性氧(ROS),这与脂质过氧化的诱导平行。这种明显的氧化应激在测量的细胞活力或功能参数中并未体现。仅在较高浓度的H2O2作用下,细胞毒性、星形胶质细胞谷胱甘肽含量的降低以及线粒体功能的损害才变得明显。H2O2暴露后,发现过氧化氢酶、锰超氧化物歧化酶和谷胱甘肽过氧化物酶的表达水平升高,而铜/锌超氧化物歧化酶的mRNA表达未受影响。这些数据表明,星形胶质细胞的AOE系统可被氧化应激直接调节,因此可能有助于保护细胞免受氧化损伤。