Involvement of the JAK-STAT Pathway and SOCS3 in the Regulation of Adiponectin-Generated Reactive Oxygen Species in Murine Macrophage RAW 264 Cells
Involvement of the JAK-STAT Pathway and SOCS3 in the Regulation of Adiponectin-Generated Reactive Oxygen Species in Murine Macrophage RAW 264 Cells
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DOI：
10.1002/jcb.22745
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发表时间：
2010-10-15
影响因子：
4
通讯作者：
Yamashita, Yoshihisa
中科院分区：
文献类型：
--
作者：
Akifusa, Sumio;Kamio, Noriaki;Yamashita, Yoshihisa
脂联素是一种由脂肪细胞分化产生的蛋白激素，被认为具有抗糖尿病和免疫抑制的特性。我们之前报道过球状形式的脂联素（gAd）诱导活性氧（ROS）和一氧化氮（NO）的产生，随后在RAW 264细胞中发生caspase依赖性凋亡细胞死亡。在这里，我们证明了gad诱导的ROS生成和细胞凋亡被细胞因子信号3抑制因子（SOCS3）所抑制。经Western blot检测，gad处理的RAW 264细胞中信号传导和转录激活因子（STAT） 3的磷酸化水平在20 min时最高。这种磷酸化被janus-activator kinase （JAK）的特异性抑制剂AG490所抑制。在RAW 264细胞中，AG490和jak -2特异性siRNA可降低gad诱导的ROS和NO。gAd刺激瞬时诱导SOCS3 mRNA表达和蛋白产生。我们检测了socs3过表达的RAW 264细胞，以研究JAK-STAT通路在gad诱导的ROS和NO生成中的作用。SOCS3过表达可显著减少ROS和NO的生成。此外，与病媒控制的转染物相比，gad诱导的caspase激活和凋亡细胞死亡在SOCS3中减少。这些结果表明，可被SOCS3表达抑制的JAK-STAT通路参与了gad诱导的ROS和NO生成以及凋亡细胞死亡。j .细胞。中国生物医学工程学报，2009,31(2):591 - 596。(c) 2010 Wiley-Liss, Inc。
Adiponectin is a protein hormone produced by differentiating adipocytes and has been proposed to have anti-diabetic and immunosuppressive properties. We previously reported that the globular form of adiponectin (gAd) induces the generation of reactive oxygen species (ROS) and nitric oxide (NO), followed by caspase-dependent apoptotic cell death in RAW 264 cells. Here, we demonstrate that gAd-induced ROS generation and apoptosis were diminished by suppressor of cytokine signaling 3 (SOCS3). The phosphorylation level of signal transducer and activator of transcription (STAT) 3 detected by Western blotting was highest at 20 min in gAd-treated RAW 264 cells. This phosphorylation was inhibited by AG490, a specific inhibitor of janus-activator kinase (JAK). The gAd-induced ROS and NO were reduced by administration of AG490 and Jak-2-specific siRNA in RAW 264 cells. The gAd stimulation transiently induced SOCS3 mRNA expression and protein production. We examined SOCS3-overexpressing RAW 264 cells to investigate the role of the JAK-STAT pathway in gAd-induced ROS and NO generation. SOCS3 overexpression significantly reduced both ROS and NO generation. Additionally, gAd-induced caspase activation and apoptotic cell death were reduced in SOCS3 transfectants compared with vector control transfectants. These results suggest that the JAK-STAT pathway, which can be suppressed by SOCS3 expression, is involved in gAd-induced ROS and NO generation followed by apoptotic cell death. J. Cell. Biochem. 111: 597-606, 2010. (c) 2010 Wiley-Liss, Inc.