Megestrol acetate inhibits the expression of cytoplasmic aromatase through nuclear C/EBPβ in reperfusion injury-induced ischemic rat hippocampus.
Global ischemia after cardiac arrest, intraoperative hypoxia/hypotension, and hemorrhagic shock causes brain injury resulting in severe neurological and neurobehavioral deficits. Neurodegeneration can be prevented by local aromatase expression, and estrogen synthesis can be neuroprotective in ischemia/reperfusion. Therefore, aromatase, the enzyme that transforms androgens to estrogens, may be a potential target for the study of reperfusion injury after brain ischemia. We investigated the expression of aromatase and C/EBPβ using western blotting in rat hippocampus after transient global ischemia plus hypotension. Immunohistochemical analysis was performed for aromatase. After 10min of ischemia, aromatase and C/EBPβ expression in cytosolic extracts were observed after 10min and 24h of reperfusion. The expression of both proteins was similar in control and damaged tissues. Immunoblot analysis demonstrated that the highest aromatase expression appeared in damaged hippocampi after 1week and was gradually reduced after 2-10weeks. C/EBPβ expression increased at 1week in nuclear extracts of damaged hippocampi. The aromatase inhibitor megestrol acetate (20mg/kg/day) suppressed aromatase and nuclear C/EBPβ levels in ischemic hippocampi. Our findings indicate that ischemia as well as chronic neurodegenerative processes leads to an increase in cytoplasmic aromatase and nuclear C/EBPβ. Thus, it is possible to hypothesize an interaction between this enzyme gene and transcription factor.
Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey. pkelicen@hacettepe.edu.tr
Pelin
P
Kelicen Ugur
Sevda
S
Lule
Mehtap
M
Cincioglu
Can
C
Pekiner
Yasemin
Y
Gursoy-Ozdemir
D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D002545:Brain Ischemia / Q000201:enzymology / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D019290:Megestrol Acetate / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D013997:Time Factors
D022782:CCAAT-Enhancer-Binding Protein-beta; D001141:Aromatase; D019290:Megestrol Acetate