Effect of hyperglycemia on the basal cytosolic free calcium level, calcium signal and tyrosine-phosphorylation in human T-cells.
In this study, we investigated the effect of in vitro hyperglycemia on the function of human T-cells (Jurkat cells). Hyperglycemic conditions caused concentration-dependent elevation of basal cytosolic free calcium level and reduced calcium signal (activation capacity), either after ionomycin or monoclonal anti-CD3 antibody treatments. Similar changes were observed if cells were treated with the calcineurin inhibitor Cyclosporin-A. We found that tyrosine-phosphorylation after anti-CD3 treatment was also impaired. High glucose concentrations in the tissue culture medium are also associated with increased non-enzymatic glycation of T-cell proteins. We propose that the increased glycation of proteins involved in calcium transport and/or intracellular signal transduction in T-cells accounts for the abnormal calcium sequestration and calcium mediated signal transduction.
Boldizsár
Ferenc
F
Department of Immunology and Biotechnology, Faculty of Medicine, University of Pécs, Pécs, Hungary. fboldizsar@hotmail.com
Berki
Timea
T
Miseta
Attila
A
Németh
Péter
P
D000911:Antibodies, Monoclonal / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000032:analysis*; D020013:Calcium Signaling / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019270:Fructosamine / Q000032:analysis; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D007700:Kinetics; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism*; D013601:T-Lymphocytes / Q000737:chemistry / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D019000:Phosphotyrosine; D019270:Fructosamine; D015759:Ionomycin; D016572:Cyclosporine; D005947:Glucose; D002118:Calcium