Involvement of mTOR in globular adiponectin-induced generation of reactive oxygen species
Involvement of mTOR in globular adiponectin-induced generation of reactive oxygen species
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DOI：
10.3109/10715760903348328
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发表时间：
2010-02-01
影响因子：
3.3
通讯作者：
Yamashita, Yoshihisa
中科院分区：
文献类型：
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作者：
Fujimoto, Akie;Akifusa, Sumio;Yamashita, Yoshihisa
球状脂联素（gAd）诱导小鼠巨噬细胞系RAW 264产生活性氧（ROS）和一氧化氮（NO）。本研究探讨了哺乳动物雷帕霉素靶蛋白（mTOR）在gad诱导的ROS和NO生成中的作用。gAd刺激诱导mTOR磷酸化，磷酸化在20min达到峰值并迅速溶解。用wortmannin抑制磷脂酰肌醇3-激酶活性可抑制gad诱导的Akt和mTOR磷酸化。雷帕霉素部分减少了gad诱导的细胞内和线粒体ROS的产生，但没有减少NO的释放。为了进一步证实mTOR在gAd刺激中的作用，我们检测了amp活化蛋白激酶（AMPK）激活剂对gAd诱导的mTOR磷酸化的影响。用AICAR、2-脱氧-d -葡萄糖和A-769662三种AMPK激活剂预处理，可抑制gad诱导的mTOR磷酸化。此外，这些AMPK激活剂显著减少了gad引起的细胞内和线粒体内ROS的产生和NO的释放。
Globular adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO) in the murine macrophage cell line RAW 264. This study investigated the role of the mammalian target of rapamycin (mTOR) in gAd-induced ROS and NO generation. gAd stimulation induced phosphorylation of mTOR, which peaked at 20 min and dissolved rapidly. Inhibition of phosphatidylinositol 3-kinase activity with wortmannin suppressed gAd-induced phosphorylation of Akt and mTOR. Administration of rapamycin partially reduced gAd-induced generation of intracellular and mitochondrial ROS, but not release of NO. To further confirm the role of mTOR in gAd stimulation, the effect of the activators of AMP-activated protein kinase (AMPK) on gAd-induced mTOR phosphorylation was examined. Pre-treatment with three kinds of AMPK activators, AICAR, 2-deoxy-D-glucose and A-769662, suppressed gAd-induced mTOR phosphorylation. Furthermore, these AMPK activators significantly reduced gAd-evoked intracellular and mitochondrial ROS generation and NO release.