Elucidation of the cell protective mechanism of acetylcholinesterase variants in cardiomyocyte and approach to therapy for myocardial infarction
| Project/Area Number |
18K15850
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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 53020:Cardiology-related
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| Research Institution | Kochi University |
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Principal Investigator |
Todaka Hiroshi 高知大学, 教育研究部医療学系基礎医学部門, 助教 (80769662)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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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 | AChE / AChE-R / 細胞保護作用 / 虚血ストレス / 心筋細胞 / 虚血性心疾患 / 細胞保護 / アセチルコリンエステラーゼ / アセチルコリン / 虚血 / 再灌流障害 |
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| Outline of Final Research Achievements |
Acetylcholinesterase (AChE), an enzyme acting on rapid acetylcholine hydrolysis, expresses in the central and peripheral nervous system. Recently, it is reported that the expression of alternative splicing variants of AChE is elevated by multiple stress in the non-neural cell and are involved in the cell protection. However, the function of AChE variants in cardiomyocyte under ischemic stress remained unclear. In the present study, we found that the expression of readthrough-AChE (AChE-R) variant was increased in cardiomyocyte under ischemic stress. Furthermore, overexpression of AChE-R in the cardiomyocyte suppressed cell death under ischemic stress through the repression of apoptosis related-proteins levels. These results suggest that AChE-R may have a role to play in the cardioprotection under ischemic stress.
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| Academic Significance and Societal Importance of the Research Achievements |
現代の虚血性心不全の治療においては、心筋保護療法の重要性が認識されつつある。本研究より心臓AChE-Rが虚血ストレス刺激に対して細胞保護に作用することが見出された。さらに心筋細胞へのAChE-Rの遺伝子導入は、細胞保護作用の増強を促した。以上の結果より、AChE-Rの遺伝子導入は虚血性心不全の病態改善および予後改善が期待され、虚血性心不全への新規治療法開発の足掛かりになると想定される。
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Report
(4 results)
Research Products
(13 results)
