LY294002 inhibits LPS-induced NO production through a inhibition of NF-κB activation:: independent mechanism of phosphatidylinositol 3-kinase
LY294002 inhibits LPS-induced NO production through a inhibition of NF-κB activation:: independent mechanism of phosphatidylinositol 3-kinase
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DOI：
10.1016/j.imlet.2004.12.007
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Kwon, TK
中科院分区：
文献类型：
--
作者：
Kim, YH;Choi, KH;Kwon, TK
磷脂酰肌醇3-激酶（PI 3 K）是细胞增殖和存活的关键因素。研究了磷脂酰肌醇3激酶（PI 3 K）抑制剂LY 294002和渥曼青霉素对脂多糖（LPS）诱导的Raw 264.7细胞一氧化氮（NO）生成和诱导型一氧化氮合酶（iNOS）表达的影响。在25 μ M LY 294002或0.5 μ M渥曼青霉素时，LPS诱导的蛋白激酶B（PKB，Akt）磷酸化受到显著抑制。在相同浓度下，LY 294002，但不是渥曼青霉素，显着抑制NO的产生和iNOS的表达。LY 294002的失活类似物LY 303511也抑制NO的产生和iNOS的表达。此外，LY 294002和LY 303511显著抑制NF-κ B的DNA结合活性和NF-κ B依赖性报告基因的表达。这些结果表明，LY 294002至少部分地通过抑制NF-κ B活化来抑制iNOS表达，而不依赖于PI 3 K。(c)2004 Elsevier B. V.保留所有权利。
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 mu M LY294002 or 0.5 mu M 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-kappa B and NF-kappa B dependent reporter gene expression. These results suggest that LY294002 inhibits iNOS expression at least in part via inhibition of NF-kappa B activation, independent of PI3K. (c) 2004 Elsevier B.V. All rights reserved.