Effects of age and dexamethasone treatment on glucocorticoid response element and activating protein-1 binding activity in rat brain.
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.
Terzic
Natasa
N
Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences VINCA, Belgrade, Serbia, Yugoslavia.
Vujcic
Miroslava
M
Ristic-Fira
Aleksandra
A
Krstic-Demonacos
Marija
M
Milanovic
Desanka
D
Kanazir
Dusan T
DT
Ruzdijic
Sabera
S
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D011965:Receptors, Glucocorticoid; D018808:Transcription Factor AP-1; D003907:Dexamethasone