The dynamic localization of the glucocorticoid receptor in rat C6 glioma cell mitochondria.
Glucocorticoids modify gene expression via the translocation of receptors from the cytosol to the nucleus following agonist-associated receptor activation. In this study, we have characterized mitochondrial glucocorticoid (GR) localization and associated translocation kinetics in the C6 mouse glioma cell line. Treatment of the cells, which were cultured in steroid-depleted culture medium, with the GR agonist dexamethasone (dex) resulted in a dramatic decrease in mitochondrial GR levels in parallel with those of the cytosolic receptor. The effect was not observed in isolated intact mitochondria suggesting that the effect is unlikely to be direct but is rather a component of the combined cellular response to GR activation. A marked stimulation of the expression of the mitochondrially-encoded cytochrome oxidase-1 (COX-1) gene was found following GR activation and its export from mitochondria. The effects were inhibited by RU486. Therefore, GR is likely to have a functional role at the level of the mitochondria within intact cells.
Koufali
Maria-M
MM
Department of Psychiatry, Ninewells Hospital, University of Dundee Medical School, Dundee, DD1 9SY, UK.
Moutsatsou
Paraskevi
P
Sekeris
Constantine E
CE
Breen
Kieran C
KC
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000737:chemistry* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics; D007700:Kinetics; D008186:Luteolytic Agents / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D008928:Mitochondria / Q000737:chemistry* / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000032:analysis* / Q000378:metabolism / Q000648:ultrastructure; D013347:Subcellular Fractions / Q000737:chemistry
D007527:Isoenzymes; D008186:Luteolytic Agents; D008565:Membrane Proteins; D011965:Receptors, Glucocorticoid; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat