Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 58:B297-B303 (2003)
© 2003 The Gerontological Society of America

Effects of Age and Dexamethasone Treatment on Glucocorticoid Response Element and Activating Protein-1 Binding Activity in Rat Brain

Natasa Terzic1, Miroslava Vujcic1, Aleksandra Ristic-Fira1, Marija Krstic-Demonacos3, Desanka Milanovic2, Dusan T. Kanazir1 and Sabera Ruzdijic2

1 Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences VINCA, Belgrade, Serbia, Yugoslavia.
2 Department of Neurobiology and Immunology, Laboratory of Molecular Neurobiology, Institute for Biological Research, Belgrade, Serbia, Yugoslavia.
3 Division of Biochemistry and Molecular Biology, University of Glasgow IBLS, Scotland, United Kingdom.

The effect of dexamethasone (DEX) on glucocorticoid receptor (GR)-mediated gene expression was examined in the brain of young and aged rats. Electrophoretic mobility shift assays showed that DEX treatment led to an increase of glucocorticoid response element (GRE) binding activity in aged rats, whereas in young animals GRE binding activity was decreased. Western blot analysis and reverse transcriptase polymerase chain reaction confirmed that, in aged animals, the GR mRNA and the GR protein levels were increased on DEX treatment. The binding activity of GRE activating protein-1 (AP-1) site and cross-competition analysis demonstrated specific pattern of expression during the ageing and DEX treatment, suggesting that GR modulates the activity of transcription factors AP-1 (Fos/Jun proteins) through protein–protein interaction. On the basis of these results, it can be concluded that the composition of transcriptional complexes that bind to GRE and AP-1 regulatory elements changes upon DEX treatment in an age-specific manner.






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