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首页> 外文期刊>The European Journal of Neuroscience >Anti-inflammatory antioxidants attenuate the expression of inducible nitric oxide synthase mediated by advanced glycation endproducts in murine microglia.
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Anti-inflammatory antioxidants attenuate the expression of inducible nitric oxide synthase mediated by advanced glycation endproducts in murine microglia.

机译:抗炎抗氧化剂可减轻鼠小胶质细胞中晚期糖基化终产物介导的诱导型一氧化氮合酶的表达。

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摘要

Advanced glycation endproducts (AGEs) accumulate on long-lived protein deposits including beta-amyloid plaques in Alzheimer's disease (AD). AGE-modified amyloid deposits contain oxidized and nitrated proteins as markers of a chronic neuroinflammatory condition and are surrounded by activated microglial and astroglial cells. We show in this study that AGEs increase nitric oxide production by induction of the inducible nitric oxide synthase (iNOS) on the mRNA and protein level in the murine microglial cell line N-11. Membrane permeable antioxidants including oestrogen derivatives (e.g. 17beta-oestradiol) thiol antioxidants (e.g. (R+)-alpha-lipoic acid) and Gingko biloba extract EGb 761, but not phosphodiesterase inhibitors such as propentophylline, prevent the up-regulation of AGE-induced iNOS expression and NO production. These results indicate that oxygen free radicals serve as second messengers in AGE-induced pro-inflammatory signal transduction pathways. As this pharmacological mechanism is not only relevant for Alzheimer's disease, but also for many chronic inflammatory conditions, such membrane-permeable antioxidants could be regarded not only as antioxidant, but also as potent therapeutic anti-inflammatory drugs.
机译:晚期糖基化终产物(AGEs)会积聚在长寿命的蛋白质沉积物上,包括阿尔茨海默氏病(AD)中的β-淀粉样蛋白斑块。 AGE修饰的淀粉样蛋白沉积物含有氧化的和硝化的蛋白质,作为慢性神经炎性疾病的标志物,被活化的小胶质细胞和星形胶质细胞包围。我们在这项研究中显示,AGEs通过诱导鼠小神经胶质细胞系N-11的mRNA和蛋白质水平上的可诱导型一氧化氮合酶(iNOS)来增加一氧化氮的产生。膜渗透性抗氧化剂,包括雌激素衍生物(例如17β-雌二醇),硫醇抗氧化剂(例如(R +)-α-硫辛酸)和银杏叶提取物EGb 761,而不是磷酸二酯酶抑制剂(如原茶碱)可阻止AGE诱导的iNOS的上调表达和没有生产。这些结果表明,氧自由基在AGE诱导的促炎信号转导途径中充当第二信使。由于这种药理学机制不仅与阿尔茨海默氏病有关,而且与许多慢性炎性疾病有关,因此这种可透过膜的抗氧化剂不仅可以被视为抗氧化剂,而且可以被视为有效的治疗性抗炎药。

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