沃特曼宁
LY294002型
磷脂酰肌醇
一氧化氮
PI3K/AKT/mTOR通路
一氧化氮合酶
蛋白激酶B
化学
激酶
NF-κB
细胞生物学
信号转导
分子生物学
生物
内分泌学
作者
Young Ho Kim,Kyung‐Sik Choi,Jong‐Wook Park,Taeg Kyu Kwon
标识
DOI:10.1016/j.imlet.2004.12.007
摘要
Phosphatidylinositol 3-kinase (PI3K) is critical player in cell proliferation and survival. The effects of LY294002 and wortmannin, inhibitors of PI3K, on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipoploysaccharide (LPS)-induced Raw 264.7 cells were investigated. Significant inhibition of LPS-induced protein kinase B (PKB, Akt) phosphorylation occurred at 25 microM LY294002 or 0.5 microM wortmannin. At the same concentrations, LY294002, but not wortmannin, significantly inhibited NO production and iNOS expression. LY303511, an inactive analogue of LY294002, also inhibited NO production and iNOS expression. In addition, LY294002 and LY303511 significantly inhibited the DNA binding activity of NF-kappaB and NF-kappaB dependent reporter gene expression. These results suggest that LY294002 inhibits iNOS expression at least in part via inhibition of NF-kappaB activation, independent of PI3K.
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