Inducible Nitric Oxide Synthase: Regulation Subserves Function
Nitric oxide synthase (iNOS) was purified (Stuehr et al. 1991) and cloned (Xie et al. 1992) from interferon-γ (IFNγ)- and lipopolysaccharide (LPS)-activated mouse macrophages. The primary structure, deduced from the cDNA and confirmed by HPLC-electrospray ionisation mass spectrometry, established that this inducible enzyme differs from the constitutive NOSs (cNOSs) cloned from cerebellar and endothelial libraries. Western blotting detected a highly similar enzyme in a wide variety of cell types after activation, including cardiac myocytes, where NO appeared to suppress rhythmicity (Roberts et al. 1992). Southern blotting and genomic cloning (Chartrain et al.1994) strongly suggest that there is a single iNOS gene. Thus, iNOS is a unique gene that can be expressed widely following activation.
KeywordsNitric Oxide Upstream Regulatory Region iNOS Promoter Distinct Gene Product Pure iNOS
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