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International Immunology Advance Access originally published online on September 7, 2009
International Immunology 2009 21(11):1269-1276; doi:10.1093/intimm/dxp093
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© The Japanese Society for Immunology. 2009. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Mitochondrial translocation of the glucocorticoid receptor in double-positive thymocytes correlates with their sensitivity to glucocorticoid-induced apoptosis

Gergely Talabér1, Ferenc Boldizsár1, Domokos Bartis1, László Pálinkás1, Mariann Szabó1, Gergely Berta2, György Sétáló, Jr2, Péter Németh1 and Timea Berki1

1 Department of Immunology and Biotechnology
2 Department of Medical Biology, Faculty of Medicine, University of Pecs, Szigeti ut. 12, Hungary

Correspondence to: F. Boldizsár; E-mail: fboldizsar{at}gmail.com

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.

Keywords: apoptosis, double-positive thymocytes, glucocorticoid hormone, glucocorticoid receptor, mitochondria

Transmitting editor: A. Falus

Received 10 June 2009, accepted 20 August 2009.


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