Dexamethasone-induced thymocytes apoptosis requires glucocorticoid receptor nuclear translocation but not mitochondrial membrane potential transition.
Dexamethasone (DEX), a glucocorticoid hormone (GCH) with specificity for the glucocorticoid receptor (GR) induces T lymphocyte and thymocyte apoptosis. DEX-activated thymocyte apoptosis requires a sequence of biochemical events including mRNA and protein synthesis. In particular, GCH treatment induces non-genomic mechanisms, such as for example Ca(2+) mobilization and PI-PLC activation, and genomic mechanisms. Most of these events, including protein synthesis, are required and precede caspase activation. As protein synthesis is required for caspases and apoptosis activation, DEX-induced GR nuclear translocation is necessary for apoptosis. Cell treatment with geldanamycin (GA) inhibits the GR nuclear translocation and consequently, caspases activation and apoptosis. Although DEX treatment induces loss of mitochondrial membrane potential (deltapsim) and cytochrome c release, deltapsim induction does not correlate with thymocyte apoptosis. In fact, while Cyclosporin-A and the caspase-9 inhibitor, Z-LEHD-FMK, inhibit DEX-induced deltapsim, do not influence apoptosis. These data indicate many biochemical events and are activated by DEX treatment of thymocytes and some, but not all, are required for apoptosis.
Marchetti
Maria Cristina
MC
Department of Clinical and Experimental Medicine, University of Perugia, via del Giochetto, 06122 Perugia, Italy.
Marco
Barbara Di
BD
Santini
Maria Cristina
MC
Bartoli
Andrea
A
Delfino
Domenico Vittorio
DV
Riccardi
Carlo
C
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D053148:Caspase 3; D020169:Caspases