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 Ca2+ 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 (Δψm) and cytochrome c release, Δψm induction does not correlate with thymocyte apoptosis. In fact, while Cyclosporin-A and the caspase-9 inhibitor, Z-LEHD-FMK, inhibit DEX-induced Δψm, 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.

Dexamethasone-induced thymocytes apoptosis requires glucocorticoid receptor nuclear translocation but not mitochondrial membrane potential transition

MARCHETTI, Maria Cristina;DI MARCO, BARBARA;BARTOLI, Andrea;DELFINO, Domenico Vittorio;RICCARDI, Carlo
2003

Abstract

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 Ca2+ 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 (Δψm) and cytochrome c release, Δψm induction does not correlate with thymocyte apoptosis. In fact, while Cyclosporin-A and the caspase-9 inhibitor, Z-LEHD-FMK, inhibit DEX-induced Δψm, 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.
2003
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11391/150175
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 18
  • ???jsp.display-item.citation.isi??? 18
social impact