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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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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 / アロマターゼ / 性行動 / 翻訳後調節 / 神経細胞 / 神経内分泌 / カルモジュリン依存性キナーゼ / カルシニューリン / 脱リン酸化 |
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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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Report
(5 results)
Research Products
(25 results)
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[Journal Article] Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters2015
Author(s)
Kurokawa, J., Sasano, T., Kodama, M., Li, M., Ebana, Y., Harada, N., Honda, S.-I., Nakaya, H., & Furukawa, T.
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Journal Title
J. Toxicol. Sci.
Volume: 40
Issue: 3
Pages: 339-348
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Aromatase controls Sjogren syndrome-like lesions through monocyte chemotactic protein-1 in target organ and adipose tissue-associated macrophages2015
Author(s)
Iwasa A, Arakaki R, Honma N, Ushio A, Yamada A, Kondo T, Kurosawa E, Kujiraoka S, Tsunematsu T, Kudo Y, Tanaka E, Yoshimura N, Harada N, Hayashi Y, Ishimaru N.
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Journal Title
Am J Pathol
Volume: 185
Issue: 1
Pages: 151-161
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Calcineurin and CRTC2 mediate FSH and TGFbeta1 upregulation of Cyp19a1 and Nr5a in ovary granulosa cells2014
Author(s)
Lai, W. A., Yeh, Y. T., Fang, W. L., Wu, L. S., Harada, N., Wang, P. H., Ke, F. C., Lee, W. L., & Hwang, J. J.
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Journal Title
J. Mol. Endocrinol.
Volume: 53
Issue: 2
Pages: 259-270
DOI
Related Report
Peer Reviewed
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