title: Nitric oxide, mitochondrial hyperpolarization, and T cell activation.
abstract: T lymphocyte activation is associated with nitric oxide (NO) production, which plays an essential role in multiple T cell functions. NO acts as a messenger, activating soluble guanyl cyclase and participating in the transduction signaling pathways involving cyclic GMP. NO modulates mitochondrial events that are involved in apoptosis and regulates mitochondrial membrane potential and mitochondrial biogenesis in many cell types, including lymphocytes. Mitochondrial hyperpolarization (MHP), an early and reversible event during both activation and apoptosis of Tlymphocytes, is regulated by NO. Here, we discuss recent evidence that NO-induced MHP represents a molecular switch in multiple T cell signaling pathways. Overproduction of NO in systemic lupus erythematosus induces mitochondrial biogenesis and alters Ca(2+) signaling. Thus, whereas NO plays a physiological role in lymphocyte cell signaling, its overproduction may disturb normal T cell function, contributing to the pathogenesis of autoimmunity.
authors.affiliation: Section of Rheumatology, Department of Medicine, Department of Microbiology, and Department of Immunology, State University of New York, Upstate Medical University, College of Medicine, Syracuse, NY 13210, USA.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Nagy
authors.forename: Agnes
authors.initials: A
authors.lastname: Koncz
authors.forename: David
authors.initials: D
authors.lastname: Fernandez
authors.forename: Andras
authors.initials: A
authors.lastname: Perl
mesh_terms: D015551:Autoimmunity; D020013:Calcium Signaling; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008213:Lymphocyte Activation; D053078:Membrane Potential, Mitochondrial; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D009569:Nitric Oxide