Kim Jiae, Kim Su-Min, Na Jung-Min, Hahn Hoh-Gyu, Cho Sung-Woo, Yang Seung-Ju
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 05505, Korea.
Department of Biomedical Laboratory Science, Konyang University, Daejeon 35365, Korea.
BMB Rep. 2016 Dec;49(12):687-692. doi: 10.5483/bmbrep.2016.49.12.169.
We recently reported the anti-inflammatory effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) on the ATP-induced activation of the NFAT and MAPK pathways through the P2X7 receptor in microglia. To further investigate the underlying mechanism of KHG26792, we studied its protective effects on hypoxia-induced toxicity in microglia. The administration of KHG26792 significantly reduced the hypoxia-induced expression and activity of caspase-3 in BV-2 microglial cells. KHG26792 also reduced hypoxia-induced inducible nitric oxide synthase protein expression, which correlated with reduced nitric oxide accumulation. In addition, KHG26792 attenuated hypoxiainduced protein nitration, reactive oxygen species production, and NADPH oxidase activity. These effects were accompanied by the suppression of hypoxia-induced protein expression of hypoxia-inducible factor 1-alpha and NADPH oxidase-2. Although the clinical relevance of our findings remains to be determined, these data results suggest that KHG26792 prevents hypoxia-induced toxicity by suppressing microglial activation. [BMB Reports 2016; 49(12): 687-692].
我们最近报道了盐酸3-(萘-2-基(丙氧基)甲基)氮杂环丁烷(KHG26792)通过小胶质细胞中的P2X7受体对ATP诱导的NFAT和MAPK信号通路激活的抗炎作用。为了进一步研究KHG26792的潜在作用机制，我们研究了其对小胶质细胞缺氧诱导毒性的保护作用。给予KHG26792可显著降低BV-2小胶质细胞中缺氧诱导的caspase-3表达和活性。KHG26792还降低了缺氧诱导的诱导型一氧化氮合酶蛋白表达，这与一氧化氮积累减少相关。此外，KHG26792减弱了缺氧诱导的蛋白质硝化、活性氧生成和NADPH氧化酶活性。这些作用伴随着缺氧诱导的缺氧诱导因子1-α和NADPH氧化酶-2蛋白质表达的抑制。尽管我们研究结果的临床相关性仍有待确定，但这些数据结果表明，KHG26792通过抑制小胶质细胞激活来预防缺氧诱导的毒性。[《BMB报告》2016年；49(12):687 - 692]
