Megestrol acetate inhibits the expression of cytoplasmic aromatase through nuclear C/EBP beta in reperfusion injury-induced ischemic rat hippocampus


Ugur P. K. , LÜLE S. , Cincioglu M. , PEKİNER C. , Gursoy-Ozdemir Y.

EUROPEAN JOURNAL OF PHARMACOLOGY, cilt.654, sa.3, ss.217-225, 2011 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 654 Konu: 3
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1016/j.ejphar.2010.11.001
  • Dergi Adı: EUROPEAN JOURNAL OF PHARMACOLOGY
  • Sayfa Sayıları: ss.217-225

Özet

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/EBP beta using western blotting in rat hippocampus after transient global ischemia plus hypotension. Immunohistochemical analysis was performed for aromatase. After 10 min of ischemia, aromatase and C/EBP beta expression in cytosolic extracts were observed after 10 min and 24 h 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 1 week and was gradually reduced after 2-10 weeks. C/EBP beta expression increased at 1 week in nuclear extracts of damaged hippocampi. The aromatase inhibitor megestrol acetate (20 mg/kg/day) suppressed aromatase and nuclear C/EBP beta 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/EBP beta. Thus, it is possible to hypothesize an interaction between this enzyme gene and transcription factor. (C) 2010 Elsevier B.V. All rights reserved.