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The high‐output nitric oxide pathway: role and regulation
Author(s) -
Xie Qiaowen,
Nathan Carl
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.56.5.576
Subject(s) - nitric oxide synthase , nitric oxide , biology , cycloheximide , calmodulin , transcription factor , gene isoform , transcription (linguistics) , lipopolysaccharide , microbiology and biotechnology , gene , biochemistry , enzyme , immunology , protein biosynthesis , endocrinology , linguistics , philosophy
Nitric oxide synthase (NOS) catalyzes the production of nitric oxide (NO), a short‐lived radical gas with physiological or pathophysiological roles in nearly every organ system. The inducible NO synthase (iNOS) is a high‐output isoform compared to the two constitutive NOSs. The iNOS from murine macrophages tightly binds calmodulin as a subunit, and its activity is not dependent on exogenous calmodulin or elevated calcium. This iNOS is induced at the transcriptional level by bacterial lipopolysaccharide (LPS) and interferon‐ γ . The promoter region of the murine iNOS gene contains at least 24 oligonucleotide motifs corresponding to elements involved in the binding of transcription factors in the promoters of other cytokine‐inducible genes. Nuclear factor NF‐ x B/c‐rel, interacting with cycloheximide‐sensitive protein(s) and binding to the NF‐ x Bd site in the iNOS promoter, controls the induction of iNOS by LPS. However, iNOS is also regulated posttranscriptionally. Complex regulation of iNOS at multiple levels may reflect the dual role of iNOS in host defense and autotoxicity. J. Leukoc. Biol. 56: 576–582; 1994.