2021 Fiscal Year Final Research Report
A study of mitochondrial function on the mechanisms of heartbeat initiation in embryonic heart
| Project/Area Number |
19K07286
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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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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
佐藤 達也 札幌医科大学, 医学部, 助教 (40592473)
一瀬 信敏 札幌医科大学, 医学部, 助教 (60448610)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 胎児心臓 / 心臓代謝 / ミトコンドリア機能 / サルコメア構造 |
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| Outline of Final Research Achievements |
The initiation of heartbeat is an essential step in cardiogenesis in the heart primordium, but it remains unclear how intracellular metabolism responds to increased energy demands after heartbeat initiation. Myofibrillogenesis is an essential process for cardiogenesis and is closely related to excitation-contraction coupling and the maintenance of heartbeat. However, how myofibrils and sarcomeres are associated with heartbeat initiation in the early embryonic heart development also remains unclear. In our study, it is suggested that the HIF-1α-mediated enhancement of glycolysis with activation of the pentose phosphate pathway, potentially leading to antioxidant defense and nucleotide biosynthesis, covers the increased energy demand in the beating heart. And it is also suggested that heartbeat initiation can be induced by development of bundles of myofilaments with up-regulated proteins associated with myofibrillogensis, whereas sarcomeres are not required for the initial heartbeat.
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| Free Research Field |
生理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、生命の源と言える心拍動開始のメカニズムを、実際の心筋細胞を用い、エネルギー代謝の観点から明らかにするものであり、心臓拍動開始前後といった、心筋細胞への分化が決定される重要な時期に、実際の心臓における心臓拍動維持に必要な機構を解明することで再生医療の発展にも寄与できる。また、低酸素環境下でも自動能を維持する心筋細胞の仕組みが分かれば、洞不全症候群など疾患の新しい治療法の開発にも繋がる可能性がある。以上より、本研究は今後臨床応用が期待されている再生医療に実際の心臓の生理学的知見の提供という貢献を行うことができ、独自性・独創性が高く研究価値が高いと考える。
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