Regulatory mechanism of Ca2+/calmodulin-dependent protein kinase IV by reactive oxygen species
| Project/Area Number |
18K14853
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 46030:Function of nervous system-related
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| Research Institution | Tohoku University (2019)
Showa Pharmaceutical University (2018) |
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Principal Investigator |
Takata Tsuyoshi 東北大学, 医学系研究科, 学術研究員 (20733257)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | カルモデュリンキナーゼ / 活性酸素 / 酸化修飾 / リン酸化修飾 / カルシウムシグナル / レドックスシグナル / 酸化ストレス / cAMP応答配列結合タンパク質 / 過酸化水素 / 小胞体ストレス / 細胞内情報伝達 |
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| Outline of Final Research Achievements |
We investigated the mechanism of calmodulin kinase IV (CaMKIV) and its effect on intracellular signal transduction pathways. We found that hydrogen peroxide (H2O2) limit CaMKIV activity at the active-site Cys residue through oxidation and downstream signaling in cells. Additionally, the Ca2+ influx-induced phospho-Thr196 of endogenous CaMKIV was also inhibited upon treatment with H2O2 in Jurkat T-lymphocytes and cerebellar granule cells. Phosphorylation of cyclic AMP response element-binding protein (CREB) at Ser133, which is downstream of CaMKIV, was also decreased upon treatment with H2O2.
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| Academic Significance and Societal Importance of the Research Achievements |
急速に進む高齢化に伴いアルツハイマー病などの脳神経の損傷を伴う神経疾患への対応が求められている。近年、多くの精神・神経疾患の原因の１つとして活性酸素が注目されている。本研究成果は、記憶能力の維持において重要なCaMKIVと活性酸素の結びつきを直接示したものであり、加齢や神経変性疾患に伴う記憶能力の減退機構の解明・予防や治療法の開発に大きく寄与することが期待される。
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] Control of Protein Function Through Oxidation and Reduction of Persulfidated States2020
Author(s)
E Doka, T Ida, M Dagnell, Y Abiko, N C Luong, N Balog, T Takata, B Espinosa, A Nishimura, Q Cheng, Y Funato, H Miki, J M Fukuto, J R Prigge, E E Schmidt, E S J Arner, Y Kumagai, T Akaike, P Nagy
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Journal Title
Sci Adv
Volume: 6
Issue: 1
Pages: 8358-8358
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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