Received for publication August 28, 2007.
Revised November 10, 2007.
Accepted for publication December 13, 2007.

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

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 LTB4 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.

Key words: Nitric oxide, Nitric oxide synthases, Signaling network analyses, Fluorescence techniques, Immunocytochemistry, Apoptosis, Mitochondrial toxins, Overexpression, RNA/siRNA