| Nitric Oxide Synthase (NOS) catalyzes the formation of nitric oxide (NO) and citruline from L-arginine, oxygen and cofactors. Three family members have been characterized: neuronal NOS (nNOS), which is found primarily in neuronal tissue; inducible NOS (iNOS), which is induced by interferon gamma and lipopolysaccharides in the kidney and cardiovascular system; and endothelial NOS (eNOS), which is expressed in blood vessels (1). NO is a messenger molecule with diverse functions throughout the body including the maintenance of vascular integrity, homeostasis, synaptic plasticity, long-term potentiation, learning, and memory (2,3).Nitric oxide catalyzed by iNOS is involved in host defense against protozoa, bacteria, fungi and viruses. Unlike constitutively expressed eNOS and nNos, iNOS is not usually expressed in quiescent cells. iNOS is transcriptionally induced in response to bacterial endotoxins such as LPS and proinflammatory cytokines in macrophages and various other cell types. Transcription factors involved in iNOS transcription include NF-κB, AP-1 and STAT. Different signaling pathways either promote (Jak1/2, PKC, c-Raf, p38 MAP kinase and p44/42 MAP kinase) or inhibit (PI3 kinase) iNOS expression depending on stimulus and cell type (4). |
