Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/32298
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    標題: CME-1, a novel polysaccharide, suppresses iNOS expression in lipopolysaccharide-stimulated macrophages through ceramide-initiated protein phosphatase 2A activation
    作者: Sheu, Joen-Rong
    Chen, Zhih-Cherng
    Hsu, Ming-Jen
    Wang, Shwu-Huey
    Jung, Kuo-Wei
    Wu, Wei-Fan
    Pan, Szu-Han
    Teng, Ruei-Dun
    Yang, Chih-Hao
    Hsieh, Cheng-Ying
    關鍵字: CME-1
    immunomodulatory property
    protein phosphatase 2A
    ceramide
    reactive oxygen species
    日期: 2018-02
    上傳時間: 2019-11-15 15:48:37 (UTC+8)
    出版者: WILEY
    摘要: CME-1, a novel water-soluble polysaccharide purified from Ophiocordyceps sinensis mycelia, has anti-oxidative, antithrombotic and antitumour properties. In this study, other major attributes of CME-1, namely anti-inflammatory and immunomodulatory properties, were investigated. Treating lipopolysaccharide (LPS)-stimulated RAW 264.7 cells with CME-1 concentration-dependently suppressed nitric oxide formation and inducible nitric oxide synthase (iNOS) expression. In the CME-1-treated RAW 264.7 cells, LPS-induced I kappa B alpha degradation and the phosphorylation of p65, Akt and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase and p38, were reduced. Treatment with a protein phosphatase 2A (PP2A)-specific inhibitor, significantly reversed the CME-1-suppressed iNOS expression; I kappa B alpha degradation; and p65, Akt and MAPK phosphorylation. PP2A activity up-regulation and PP2A demethylation reduction were also observed in the cells. Moreover, CME-1-induced PP2A activation and its subsequent suppression of LPS-activated RAW 264.7 cells were diminished by the inhibition of ceramide signals. LPS-induced reactive oxygen species (ROS) and hydroxyl radical formation were eliminated by treating RAW 264.7 cells with CME-1. Furthermore, the role of ceramide signalling pathway and anti-oxidative property were also demonstrated in CME-1-mediated inhibition of LPS-activated primary peritoneal macrophages. In conclusion, CME-1 suppressed iNOS expression by up-regulating ceramide-induced PP2A activation and reducing ROS production in LPS-stimulated macrophages. CME-1 is a potential therapeutic agent for treating inflammatory diseases.
    link: http://dx.doi.org/10.1111/jcmm.13424
    關聯: Journal of Cellular Physiology, v.22, n.2, pp.999-1013
    显示于类别:[藥學系(所)] 期刊論文

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