Reactive oxygen species from human astrocytes induced functional impairment and oxidative damage.
Reactive oxygen species from human astrocytes induced functional impairment and oxidative damage.
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人类星形胶质细胞中的活性氧诱导功能障碍和氧化损伤。
DOI：
10.1007/s11064-013-1123-z
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发表时间：
2013-10
影响因子：
4.4
通讯作者：
Rock, R. Bryan
中科院分区：
文献类型：
--
作者：
Sheng, Wen S.;Hu, Shuxian;Feng, Amy;Rock, R. Bryan
活性氧（ROS）已被证明是衰老和疾病的贡献者。ROS还充当信号级联的触发开关，导致相应的细胞和分子事件。在中枢神经系统中，小胶质细胞可能是ROS产生的主要来源。然而，活化的星形胶质细胞似乎也能够产生ROS。在本研究中，我们研究了白细胞介素（IL）-1β和干扰素（IFN）-γ刺激人星形胶质细胞产生的ROS及其潜在的有害影响。虽然IFN-γ单独没有影响，但它以时间依赖性方式增强IL-1β诱导的ROS产生。IL-1β激活的星形胶质细胞中ROS的来源之一是线粒体中超氧化物产生增加，伴随着锰超氧化物歧化酶的增强和过氧化氢酶表达的抑制。NADPH氧化酶（NOX）也可能有助于ROS的产生，因为星形胶质细胞表达NOX同工型。谷氨酸摄取是星形胶质细胞防止兴奋性毒性的最重要方法之一，在IL-1β激活的星形胶质细胞中下调，并在IFN-γ存在下进一步抑制; IFN-γ本身发挥的作用最小。IL-1β ± IFN-γ激活的人星形胶质细胞中8-异前列烷水平升高表明下游脂质过氧化。DPI（diphenyleneiodonium）预处理可抑制IL-1β ± IFN-γ诱导的活性氧产生，恢复谷氨酸摄取功能，并使8-异前列腺素降低至接近对照水平，提示活性氧参与了活化星形胶质细胞的功能障碍。这些结果支持这样的观点，即抑制活化的人星形胶质细胞以维持氧化还原稳态对于保持其在CNS中的神经保护潜力至关重要。
Reactive oxygen species (ROS) have been shown to be a contributor to aging and disease. ROS also serve as a trigger switch for signaling cascades leading to corresponding cellular and molecular events. In the central nervous system, microglial cells are likely the main source of ROS production. However, activated astrocytes also appear to be capable of generating ROS. In this study we investigated ROS production in human astrocytes stimulated with interleukin (IL)-1β and interferon (IFN)-γ and its potential harmful effects. Although IFN-γ alone had no effect, it potentiated IL-1β-induced ROS production in a time-dependent manner. One of the sources of ROS in IL-1β-activated astrocytes was from increased superoxide production in mitochondria accompanied by enhanced manganese superoxide dismutase and inhibited catalase expression. NADPH oxidase (NOX) may also contribute to ROS production as astrocytes express NOX isoforms. Glutamate uptake, which represents one of the most important methods of astrocytes to prevent excitotoxity, was down-regulated in IL-1β-activated astrocytes, and was further suppressed in the presence of IFN-γ; IFN-γ itself exerted minimal effect. Elevated levels of 8-isoprostane in IL-1β ± IFN-γ-activated human astrocytes indicate downstream lipid peroxidation. Pretreatment with DPI (diphenyleneiodonium) abolished the IL-1β ± IFN-γ-induced ROS production, restored glutamate uptake function and reduced 8-isoprostane to near control levels suggesting that ROS contributes to the dysfunction of activated astrocytes. These results support the notion that dampening activated human astrocytes to maintain the redox homeostasis is vital to preserve their neuroprotective potential in the CNS.
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影响因子：
4.8
作者：
Guyton, KZ;Liu, YS;Holbrook, NJ
通讯作者：
Holbrook, NJ
影响因子：
9.3
作者：
Dohi K;Ohtaki H;Nakamachi T;Yofu S;Satoh K;Miyamoto K;Song D;Tsunawaki S;Shioda S;Aruga T
通讯作者：
Aruga T
DOI：
10.1038/nri3423
发表时间：
2013-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Altenhofer, Sebastian;Kleikers, Pamela W. M.;Radermacher, Kim A.;Scheurer, Peter;Hermans, J. J. Rob;Schiffers, Paul;Ho, Heidi;Wingler, Kirstin;Schmidt, Harald H. H. W.
通讯作者：
Schmidt, Harald H. H. W.
影响因子：
3.9
作者：
Beak, SM;Lee, YS;Kim, JA
通讯作者：
Kim, JA