2016 Fiscal Year Final Research Report
Post-translational dual regulation of cytochrome P450 aromatase responsible for non-genomic actions of estrogens
| Project/Area Number |
25461398
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Fujita Health University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Keywords | エストロゲン / 非遺伝子作用 / 翻訳後修飾 / リン酸化 / ユビキチン化 / プロテアソーム |
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| Outline of Final Research Achievements |
Post-translational acute regulation of aromatase responsible for non-genomic actions of estrogens was studied. Microsomal aromatase in JEG-3 cells was rapidly inactivated and subsequently degraded in the presence of cytosol fraction, calcium, and ATP. Experiments using various kinase and phosphatase inhibitors, and siRNAs indicated that aromatase is regulated acutely at the catalytic level and subsequently at the enzyme content level by phosphorylation/dephosphorylation.
In nerve cells, a major site of non-genomic actions of estrogens, aromatase activity was suppressed within 10 min after glutaminergic stimulations, whereas it was enhanced by GABAergic, noradrenergic, and serotonergic stimulations. The degradation was suppressed by proteasome inhibitor, MG132. The knockdown and siRNA inhibition revealed the involvement of ER-associated heat shock protein/ubiquitination and then proteasome systems in the rapid degradation of the phosphorylated aromatase in nerve cells.
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| Free Research Field |
生化学
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