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

Kalipada Pahan, Xiaojuan Liu, Charles Wood, John R. Raymond

Research output: Contribution to journalArticle

32 Scopus citations

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. Copyright (C) 2000 Federation of European Biochemical Societies.

Original languageEnglish (US)
Pages (from-to)203-207
Number of pages5
JournalFEBS Letters
Volume472
Issue number2-3
DOIs
StatePublished - Apr 28 2000

Keywords

  • Astrocyte
  • Cytokine
  • Inducible nitric oxide synthase
  • NF-kB
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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