title: Indinavir inhibits the expression of cytoplasmic aromatase and nuclear SREBP in the hippocampus of reperfusion injury-induced ischemic rats.
abstract: Ischemic brain injury due to insults, such as stroke, is a leading cause of severe neurological and neurobehavioral deficits and death. 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 sterol regulatory element binding protein (SREBP) using Western blotting in the rat hippocampus after transient global ischemia plus hypotension. After 10 min of ischemia, aromatase and SREBP expression was observed in cytosolic extracts after 1, 4 and 10 weeks of reperfusion. Previous immunoblot analysis demonstrated that the highest aromatase expression appeared in damaged hippocampi after 1 week. In this study, SREBP expression was increased at 1 week in the nuclear extracts of damaged hippocampi. The aromatase inhibitor megestrol acetate (20 mg/kg/day; 21 days) and the SREBP inhibitor indinavir (15 mg/kg/day; 30 days) suppressed aromatase levels in ischemic hippocampi. Our findings indicate that ischemia, as well as chronic neurodegenerative processes, leads to an increase in cytoplasmic aromatase and nuclear SREBP. Thus, it is possible to hypothesize that an interaction between this enzyme gene and the transcription factor exists.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Turkey.
authors.forename: Mehtap
authors.initials: M
authors.lastname: Cincioglu
authors.forename: Gorkem
authors.initials: G
authors.lastname: Kismali
authors.forename: Sedat Askin
authors.initials: SA
authors.lastname: Ugur
authors.forename: Pelin
authors.initials: P
authors.lastname: Kelicen-Ugur
mesh_terms: D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D047072:Aromatase Inhibitors / Q000494:pharmacology; D002545:Brain Ischemia / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D003593:Cytoplasm / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D019469:Indinavir / Q000494:pharmacology*; D008297:Male; D019290:Megestrol Acetate / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism*; D051779:Sterol Regulatory Element Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D047072:Aromatase Inhibitors; D051779:Sterol Regulatory Element Binding Proteins; D019469:Indinavir; D001141:Aromatase; D019290:Megestrol Acetate