Inhibition of inducible nitric-oxide synthase protects human T cells from hypoxia-induced apoptosis

Armed Forces Radiobiology Research Institute, Bldg. 46, Room 2423, 8901 Wisconsin Ave., Bethesda, MD 20889-5603, USA.
Molecular pharmacology (Impact Factor: 4.12). 04/2008; 73(3):738-47. DOI: 10.1124/mol.107.041079
Source: PubMed

ABSTRACT Sodium cyanide-induced chemical hypoxia triggers a series of biochemical alterations leading to apoptosis in many cell types, including T cells. It is known that chemical hypoxia promotes inducible nitric-oxide synthase (iNOS) gene transcription by activating its transcription factors. To determine whether iNOS and NO production are responsible for chemical hypoxia-induced apoptosis, we exposed human Jurkat T cells to sodium cyanide in the presence or absence of iNOS inhibitors. We found that iNOS expression is necessary for hypoxia-induced lipid peroxidation and leukotriene B(4) generation. The inhibition of iNOS limited T-cell apoptosis by decreasing the activity of caspase-3 without affecting the expression of Fas/Apo-1/CD95 on the surface membrane of T cells. These data suggest iNOS-mediated NO produced endogenously in the T cell alters overall T-cell function and results in apoptosis. Proper control of iNOS expressed in the T cell may represent a useful approach to immunomodulation.

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