Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells with oxidized LDL
Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells with oxidized LDL
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DOI：
10.1016/j.bbrc.2004.01.049
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发表时间：
2004-03-05
影响因子：
3.1
通讯作者：
Goldstein, BJ
中科院分区：
文献类型：
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作者：
Motoshima, H;Wu, XD;Goldstein, BJ
脂联素（也称为30-kDa脂肪细胞补体相关蛋白或Acrp 30）是一种丰富的脂肪细胞来源的血浆蛋白，具有抗动脉粥样硬化和胰岛素增敏特性。为了探讨脂联素血管保护作用的可能机制，我们采用体外培养的牛内皮细胞（BAECs），研究了重组脂联素球状体（gAd）对氧化低密度脂蛋白（oxLDL）诱导的BAECs增殖和活性氧（ROS）产生的影响。通过RT-PCR，我们发现BAECs优先表达AdipoR 1，gAd的高亲和力受体。用oxLDL（10 μ g/ml）处理BAECs 16小时可刺激细胞增殖约60%，而与gAd共孵育可抑制细胞增殖。用gAd处理细胞还抑制基础和oxLDL诱导的超氧化物释放，并抑制oxLDL对p42/p44 MAP激酶的激活。gAd的作用被特异性多克隆抗脂联素抗体（TJ 414）阻断。NAD（P）H氧化酶抑制剂DPI（diphenyleneiodonium）可抑制OxLDL诱导的BAEC增殖和超氧阴离子释放，eNOS抑制剂L-nitroarginine methyl ester（L-NAME）则无此作用。最后，gAd改善了oxLDL对eNOS活性的抑制。这些数据表明，gAd抑制oxLDL诱导的细胞增殖和抑制细胞超氧化物生成，可能通过NAD（P）H氧化酶连接的机制。(C)2004年爱思唯尔公司All rights reserved.
Adiponectin (also known as 30-kDa adipocyte complement-related protein or Acrp30) is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties. In order to investigate the potential mechanism(s) of the vascular protective effect of adiponectin, we used cultured bovine endothelial cells (BAECs) to study the effect of recombinant globular adiponectin (gAd) on cellular proliferation and the generation of reactive oxygen species (ROS) induced by oxidized LDL (oxLDL). By RT-PCR, we found that BAECs preferentially express AdipoR1, the high-affinity receptor for gAd. Treatment of BAECs with oxLDL (10 mug/ml) for 16 h stimulated cell proliferation by similar to60%, which was inhibited by co-incubation with gAd. Cell treatment with gAd also inhibited basal and oxLDL-induced superoxide release, and suppressed the activation of p42/p44 MAP kinase by oxLDL. The effects of gAd were blocked by a specific polyclonal anti-adiponectin antibody (TJ414). OxLDL-induced BAEC proliferation and superoxide release were inhibited by the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), but not the eNOS inhibitor L-nitroarginine methyl ester (L-NAME). Finally, gAd ameliorated the suppression of eNOS activity by oxLDL. These data indicate that gAd inhibits oxLDL-induced cell proliferation and suppresses cellular superoxide generation, possibly through an NAD(P)H oxidase-linked mechanism. (C) 2004 Elsevier Inc. All rights reserved.