[Signal transduction abnormalities in systemic lupus erythematosus].
Engagement of T cell receptors by antigen-presenting cells or stimulation by cytokines determine whether the cell will become activated, anergic or die via apoptosis or necrosis. Ca2+ is a key second messenger that delivers signal from the cell surface, reactive oxygen intermediates and nitric oxide are recently recognized as important mediators of T cell activation. Nitric oxide is a multifunctional intracellular and intercellular messenger induces mitochondrial biogenesis in many cell types, such as lymphocytes. Mitochondria produce reactive oxygen intermediates and store and release Ca2+ in response to activation and death signals. Rapid Ca2+ fluxing is increased while sustained Ca2+ signaling is decreased in lupus T cells. Lupus T cells contain increased numbers and mass of mitochondria. Serum nitric oxide levels and production of nitric oxide by monocytes is increased in patients with systemic lupus erythematosus. Lupus T cells exhibit mitochondrial hyperpolarization and increased mitochondrial mass, which confer predisposition to necrosis rather than apoptosis in response to repetitive activation and death signals. Exposure of normal T cells to nitric oxide dose-dependently increase the mitochondrial mass and mimic rapid and sustained Ca2+ signal abnormalities observed in lupus T cells. Thus increased mitochondrial biogenesis may account for altered Ca2+ handling and represents novel targets for pharmacological intervention in SLE.
Nagy
György
G
Semmelweis Egyetem, Altalános Orvostudományi Kar, 111. Belgyógyászati Klinika Reumatológiai es Fizioterápiás Tanszéki Csoport, I. Részleg, Budai Irgalmasrendi Kórház, Budapest.
Géher
Pál
P
Koncz
Agnes
A
Perl
András
A
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008213:Lymphocyte Activation; D008928:Mitochondria / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D015220:Calcium Channels; D009569:Nitric Oxide; D002118:Calcium