Description
Nitric oxide (NO) is a colorless, free radical gas that carries a variety of messages between cells. Vasorelaxation,
neurotransmission and cytotoxicity can all be potentiated through cellular response to NO. NO production is mediated by members of the nitric oxide synthase (NOS) family including the two constitutive isoforms: brain, bNOS, or neuronal NOS,
nNOS (type I) and endothelial cell NOS,
eNOS (type III); along with the inducible isoform,
iNOS (type II). NOS catalyzes the oxidization of L-arginine to produce L-citrulline and NO, requiring the cofactors
calmodulin, nicotinamide adenine dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), and flavin mononucleotide (FMN),
heme, and
tetrahydrobiopterin (1).
The 131 kDa enzyme, iNOS, is found in a variety of cell types including macrophages, hepatocytes, synoviocytes, and smooth muscle cells. While constitutively expressed in kidneys, in other tissues iNOS is induced by bacterial lipopolysaccharides (LPS), growth factors, and
cytokines such as
IFN-gamma,
TNF,
IL-1 and
IL-2. iNOS is not regulated by the level of intracellular Ca2+ and is constantly active as a dimer when expressed. iNOS activity is elevated in a variety of diseases including atherosclerosis, heart failure, sepsis, solid tumors, and
type 2 diabetes. Acting as a critical mediator of
inflammation and
apoptosis, iNOS inhibitors have been shown to alleviate obesity and stress inducted insulin resistance in mouse models (2,3).
References
1. Forstermann U, and Sessa WC. (2012) Nitric oxide synthases: regulation and function. Eur Heart J. 33(7): 829-837. PMID: 21890489
2. Aktan F. (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci. 75(6):639-53. PMID: 15172174
3. Cinelli MA, Do HT, Miley GP, Silverman RB. (2020) Inducible nitric oxide synthase: Regulation, structure, and inhibition. Med Res Rev. 40(1):158-189. PMID: 31192483
Bioinformatics
| Entrez |
Human Mouse Rat |
| Uniprot |
|
| Product By Gene ID |
4843 |
| Alternate Names |
- EC 1.14.13.39
- Hepatocyte NOS
- HEP-NOS
- Inducible NO synthase
- Inducible NOS
- iNOS
- nitric oxide synthase 2, inducible
- nitric oxide synthase 2A (inducible, hepatocytes)
- nitric oxide synthase, inducible
- nitric oxide synthase, macrophage
- NOS type II
- NOS
- NOS2
- NOS2A
- Peptidyl-cysteine S-nitrosylase NOS2
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