Regulation of the Expression of the Inducible Isoform of Nitric Oxide Synthase

Csaba Szabó, Christoph Thiemermann

    Research output: Contribution to journalArticle

    93 Scopus citations

    Abstract

    All forms of NOS contain four prosthetic groups: flavin-adenine dinucleotide; flavin mononucleotide, tetrahydrobiopterin (BH4), and a heme complex, iron protoporphyrin IX. All NOS isoforms are dependent on calmodutin; in the inducible isoform calmodulin is already present in a tightly bound form. The role of calmodulin is to control the electron transfer from NADPH to the flavins, possibly by causing a reorientation of the reductase and oxygenase domains of NOS, perhaps moving them into a favorable position for electron transfer among them. The function of BH4 is unclear, but may substitute for peroxy-heme to carry out nucleophilic attack on hydroxyarginine or perhaps may act as a stabilizer of the active structure of NOS—that is, assembling dimeric forms of NOS in the case of bNOS and iNOS. The cellular and molecular mechanisms of iNOS induction, or its inhibition by pharmacological agents, are not fully understood. They clearly involve transcription of mRNA and novel protein biosynthesis and take at least several hours. The sequencing of the DNA regions upstream of the iNOS gene (that is, the promoter regions) revealed separate promoter regions for the induction of iNOS by endotoxin and interferon-γ (IFN-γ).

    Original languageEnglish (US)
    Pages (from-to)113-153
    Number of pages41
    JournalAdvances in Pharmacology
    Volume34
    Issue numberC
    DOIs
    StatePublished - Jan 1 1995

    ASJC Scopus subject areas

    • Pharmacology

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