Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL-6 signaling pathway in rat primary adipocytes.
Oligonol, an oligomerized lychee fruit-derived polyphenol, activates the Ras/Raf-1/MEK1/2 cascade independent of the IL-6 signaling pathway in rat primary adipocytes.
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DOI：
10.1016/j.bbrc.2010.10.082
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发表时间：
2010-11
影响因子：
3.1
通讯作者：
J. Ogasawara;K. Kitadate;H. Nishioka;H. Fujii;T. Sakurai;T. Kizaki;T. Izawa;H. Ishida;M. Tanno;H. Ohno
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文献类型：
--
作者：
J. Ogasawara;K. Kitadate;H. Nishioka;H. Fujii;T. Sakurai;T. Kizaki;T. Izawa;H. Ishida;M. Tanno;H. Ohno
Oligonol是荔枝果实衍生的低分子形式的多酚。在这项研究中，研究了Oligonol对原代脂肪细胞中丝裂原活化蛋白激酶（MAPK）信号通路的影响，以研究伴随体外脂解增加的磷酸化细胞外信号调节激酶1/2（ERK 1/2）水平升高的机制。Oligonol可显著提高Ras活化水平及Raf-1和MAPK/ERK激酶1/2（MEK 1/2）的磷酸化水平，而不增加pan-Raf-1和-MEK 1/2蛋白。用选择性Raf-1抑制剂GW 5074或选择性MEK 1/2抑制剂PD 98059预处理可完全抑制Oligonol对Raf-1和MEK 1/2磷酸化的增加。IL-6还通过与其受体的结合激活脂肪细胞中的MAPK信号通路。IL-6诱导的Raf-1和MEK 1/2的磷酸化被IL-6受体抗体预处理显著抑制。然而，在这样的条件下，与未处理的对照细胞相比，用Oligonol磷酸化的Raf-1和MEK 1/2的水平仍然保持显著较高，并且脂肪细胞的IL-6分泌显著减少。这些结果表明，Oligonol激活Ras/Raf-1/MEK 1/2信号通路，独立于IL-6信号通路，导致原代脂肪细胞中ERK 1/2蛋白的激活。
Oligonol is a lychee fruit-derived low-molecular form of polyphenol. In this study, the effect of Oligonol on the mitogen activated-protein kinase (MAPK) signaling pathway in primary adipocytes was investigated to examine the mechanism underlying the enhanced levels of phosphorylated extracellular-signaling regulatory kinase1/2 (ERK1/2) that accompany an in vitro increase in lipolysis. Oligonol significantly elevated the levels of activated Ras and the phosphorylation of Raf-1 and MAPK/ERK kinase1/2 (MEK1/2) with no increase in pan-Raf-1 and -MEK1/2 proteins. The increase in phosphorylation of Raf-1 and MEK1/2 with Oligonol was inhibited completely by pretreatment with GW5074, a selective Raf-1 inhibitor, or PD98059, a selective MEK1/2 inhibitor. IL-6 also activated the MAPK signaling pathway in adipocytes through the association with its receptor. IL-6-induced phosphorylation of Raf-1 and MEK1/2 was significantly inhibited by pretreatment with the IL-6 receptor antibody. Under such a condition, however, the levels of phosphorylated Raf-1 and MEK1/2 with Oligonol still remained significantly higher, and there was a significant decrease in secretion of IL-6 from adipocytes, compared with untreated control cells. These results suggest that Oligonol activates the Ras/Raf-1/MEK1/2 signaling pathway, independent of the IL-6 signaling pathway, leading to activation of ERK1/2 proteins in primary adipocytes.