Protein kinase C-independent selective induction of nitric oxide synthase activity in rat alveolar macrophages by staurosporine

Rinat Tabakman, Philip Lazarovici, Yuzuru Matsuda, Chaya Brodie, Haim Ovadia

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    5 Scopus citations

    Abstract

    The purpose of this study was to characterize the effect of the K-252a family of protein kinase inhibitors with emphasis on staurosporine (ST), on stimulation of the inducible nitric oxide synthase activity in rat alveolar NR8383 macrophages. We found that ST, but not K-252a, K-252b, KT-5720, and KT-5823, selectively enhanced the basal or the lipopolysaccharide (LPS)induced nitric oxide production. ST-induced NO production was blocked by L-NAME, K-252a, and phosphatase inhibitors and could not be mimicked by other protein kinase C (PKC) inhibitors such as calphostine. An additive effect between ST and PMA on NO production was observed. LPS and PMA but not ST induced PKCβ translocation from the cytosol to the membrane fraction. ST may induce and affect the state of phosphorylation of iNOS via PKC-independent mechanisms. ST provides an important pharmacological tool to investigate PKC- independent signal transduction pathways which regulate iNOS, induction, and activity in rat NR8383 macrophages.

    Original languageEnglish
    Pages (from-to)250-258
    Number of pages9
    JournalNitric Oxide - Biology and Chemistry
    Volume2
    Issue number4
    DOIs
    StatePublished - Aug 1998

    Bibliographical note

    Funding Information:
    This work was partly supported by a grant from the Chief Scientist, Israel Ministry of Health (L.P) and by a Sol Irwin Juni Fund. The technical assistance of Miss F. Baicer is greatly appreciated.

    Keywords

    • Isoenzymes
    • Lipopolysaccharide
    • Macrophages
    • NR8383
    • PKC
    • Phorbol ester
    • Staurosporine
    • iNOS

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