| Project/Area Number |
17K09658
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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 |
Respiratory organ internal medicine
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
瀬戸口 靖弘 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (90206649)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | ミトコンドリア / 脱アミド化 / 加齢 / 脂肪滴 / EGF受容体 / Prohibitin 1 / mitochondria / アスパラギン酸残基 / 脱アミド / 慢性閉塞性肺疾患 / 内科 |
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| Outline of Final Research Achievements |
Amino acid sequence of Prohibitin 1(PHB1) contains two sites (N24D and N226D) prone to be non-enzymatically modulated based on the propensity of deamidation. To test the effects of mutant PHB1 on mitochondrial structure, lipid droplets structure, cell growth, we generated stable A549 cell lines with WT-PHB1 or N24D-PHB1 or N226D-PHB1. The mutant PHB1 proteins affected the fragmentation of mitochondria, increased number of larger sized lipid droplets, delayed cell growth, and earlier dephosphorylation of EGFR tyrosine kinase domain. To investigate the amino acid changes of PHB1 from Asn to Asp, we generated monoclonal antibodies against N24D PHB1, which recognized the increased alteration of PHB1 in the lung tissues from aged mice. The increased ratio of N24D PHB1 protein to WT PHB1 protein suggested that aging process of lung tissues contains nonenzymatic alteration, presumably resulting in the failure of lipid droplets formation and cell cycle progression.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではミトコンドリア蛋白質PHB1の非酵素的異性体化反応が肺で認められ、PHB1(N24D)の変化が増加し、慢性閉塞性肺疾患発症における加齢的因子の一つにミトコンドリア蛋白質異性体化の関与が確認され、慢性閉塞性肺疾患の発症におけるミトコンドリア機能の保護の重要性として禁煙の重要性の一つの根拠になると考えられる。
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