Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

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Taipei Medical University Institutional Repository > 醫學科技學院 > 醫學檢驗暨生物技術學系所 > 期刊論文 > Item 987654321/3791

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题名:	Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin
作者:	何元順;梁有志 Der-Zen Liu;Hong-Jen Liang;Chien-Ho Chen;Shyr-Yi Lin;Wen-Bin Zhong;Feng-Ming Ho;Wen-Chi Hou;Jui-Lien Lo;Yuan-Soon
贡献者:	醫學檢驗暨生物技術學系
关键词:	Phosphatidylinositol 3-kinase;Phosphoinositide-specific phospholipase C;Inducible nitric oxide synthase;Wortmannin;Lipopolysaccharide
日期:	2007
上传时间:	2009-08-25 10:39:02 (UTC+8)
摘要:	Phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway.
關聯:	Biochimica et Biophysica Acta.(173):869-879.
数据类型:	article
显示于类别:	[醫學檢驗暨生物技術學系所] 期刊論文

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