磷脂酰肌醇3激酶组成型活性形式的表达可抑制人星形胶质细胞中一氧化氮合酶的诱导。

Expression of a constitutively active form of phosphatidylinositol 3-kinase inhibits the induction of nitric oxide synthase in human astrocytes.

作者信息

Pahan K, Liu X, Wood C, Raymond J R

机构信息

Department of Oral Biology, University of Nebraska Medical Center College of Dentistry, 40th and Holdrege, Lincoln, NE 68583, USA.

出版信息

FEBS Lett. 2000 Apr 28;472(2-3):203-7. doi: 10.1016/s0014-5793(00)01465-4.

DOI:10.1016/s0014-5793(00)01465-4

PMID:10788611

Abstract

The present study underlines the importance of phosphatidylinositol 3-kinase (PI 3-kinase) in attenuating the induction of nitric oxide synthase (iNOS) in human astrocytes. Proinflammatory cytokines induced the production of nitric oxide (NO) and the expression of iNOS in human U373MG astrocytoma cells and primary astrocytes. Expression of a catalytically active p110 subunit (p110*) of PI 3-kinase but not that of a kinase-deficient mutant of p110 (p110-kd) induced an increase in PI 3-kinase activity and inhibited cytokine-induced production of NO and expression of iNOS. However, expression of p110* had no effect on the activation of NF-kB, suggesting that p110* inhibits the expression of iNOS without inhibiting the activation of NF-kB.

摘要

本研究强调了磷脂酰肌醇3激酶（PI 3激酶）在减弱人星形胶质细胞中一氧化氮合酶（iNOS）诱导方面的重要性。促炎细胞因子可诱导人U373MG星形细胞瘤细胞和原代星形胶质细胞产生一氧化氮（NO）并表达iNOS。PI 3激酶具有催化活性的p110亚基（p110*）的表达可诱导PI 3激酶活性增加，而p110的激酶缺陷突变体（p110-kd）的表达则无此作用，且p110可抑制细胞因子诱导的NO产生和iNOS表达。然而，p110的表达对NF-κB的激活没有影响，这表明p110*在不抑制NF-κB激活的情况下抑制iNOS的表达。