Inhibition of inducible nitric-oxide synthase protects human T cells from 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 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.

• Authors: Juliann G Kiang, Sandeep Krishnan, Xinyue Lu, Yansong Li
• Journal: Molecular pharmacology (Mol Pharmacol) Vol. 73 Issue 3 Pg. 738-47 (Mar 2008) ISSN: 1521-0111 [Electronic] United States
• PMID: 18079278 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• fas Receptor
• Leukotriene B4
• Nitric Oxide
• Malondialdehyde
• Nitric Oxide Synthase Type II
• Caspase 3
• Sodium Cyanide

Topics

• Apoptosis (drug effects, genetics, physiology)
• Caspase 3 (analysis, metabolism)
• Dose-Response Relationship, Drug
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Hypoxia
• Jurkat Cells
• Leukotriene B4 (analysis, biosynthesis)
• Lipid Peroxidation (drug effects)
• Malondialdehyde (analysis)
• Nitric Oxide (analysis, biosynthesis)
• Nitric Oxide Synthase Type II (antagonists & inhibitors)
• Sodium Cyanide (pharmacology)
• Statistics as Topic
• T-Lymphocytes (metabolism)
• Time Factors
• fas Receptor (metabolism)