Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/27076
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    標題: Labedipinedilol-A prevents lysophosphatidylcholine-induced vascular smooth muscle cell death through reducing reactive oxygen species production and anti-apoptosis.
    作者: Hsua, Jong-Hau
    Wu, Jiunn-Ren
    Liou, Shu-Fen
    Chen, Huai-Min
    Dai, Zen-Kong
    Chen, Ing-Jun
    Yeh, Jwu-Lai
    貢獻者: 藥學系
    關鍵字: Labedipinedilol-A
    Lysophosphatidylcholine
    Atherosclerosis
    Vascular smooth muscle cell
    Calcium
    Reactive oxygen species
    Apoptosis
    日期: 2011-08
    上傳時間: 2013-10-25 15:33:53 (UTC+8)
    出版者: Elsevier
    摘要: Objective: : Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis.

    Methods and results: : VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis. Labedipinedilol-A attenuated lysoPC-induced cell death and Ca(2+) influx. It also reduced reactive oxygen species (ROS) production evoked by lysoPC and down-regulated expressions of NAD(P) H oxidase subunits, Nox1 and Rac1. Moreover, it inhibited lysoPC-induced phosphorylation of MAPK including ERK1/2, JNK, and p38. It mitigated the dissipation of mitochondrial transmembrane potential induced by lysoPC. Lastly, labedipinedilol-A inhibited lysoPC-induced apoptosis with attenuation of caspase-3/-9 activations and modulation of Bax/Bcl-2 protein expressions.

    Conclusion: : Labedipinedilol-A can suppress lysoPC-induced VSMCs death via reducing ROS production and anti-apoptosis. These protective effects are potentially mediated through the inhibition of Ca(2+) influx, down-regulation of the NAD(P) H oxidase subunits (Nox1/Rac1) and MAPK signaling, and attenuation of mitochondrial depolarization. Thus, labedipinedilol-A may have a valuable role in the preventing atherosclerosis associated with hyperlipidemia. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
    關聯: Atherosclerosis, 217(2), pp.379-386
    顯示於類別:[藥學系(所)] 期刊論文

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