title: Mitochondrial translocation of the glucocorticoid receptor in double-positive thymocytes correlates with their sensitivity to glucocorticoid-induced apoptosis.
abstract: Glucocorticoid receptor (GR) signaling plays an important role in the selection and apoptosis of thymocytes. Besides nuclear translocation, mitochondrial translocation of the ligand-bound GR in lymphoid cells was also shown, which might determine glucocorticoid (GC)-induced apoptosis sensitivity. In the present work, we followed the ligand-induced GR trafficking in CD4+CD8+ double-positive (DP) thymocytes. Using confocal microscopy, we found that upon short-term in vitro GC analog [dexamethasone (DX)] treatment, the GR translocates into the mitochondria but not into the nucleus in DP cells. We also analyzed the GR redistribution in cytosolic, nuclear and mitochondrial fractions of unseparated thymocytes by western blot and confirmed that in DX-treated cells a significant fraction of the GR translocates into the mitochondria. DX reduced the mitochondrial membrane potential of DP cells within 30 min, measured by flow cytometry, which refers to a direct modulatory activity of mitochondrial GR translocation. The abundant mitochondrial GR found in DP cells well correlates with their high GC-induced apoptosis sensitivity.
authors.affiliation: Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Szigeti ut. 12, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Talabér
authors.forename: Ferenc
authors.initials: F
authors.lastname: Boldizsár
authors.forename: Domokos
authors.initials: D
authors.lastname: Bartis
authors.forename: László
authors.initials: L
authors.lastname: Pálinkás
authors.forename: Mariann
authors.initials: M
authors.lastname: Szabó
authors.forename: Gergely
authors.initials: G
authors.lastname: Berta
authors.forename: György
authors.initials: G
authors.lastname: Sétáló
authors.forename: Péter
authors.initials: P
authors.lastname: Németh
authors.forename: Timea
authors.initials: T
authors.lastname: Berki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone