2018 Fiscal Year Final Research Report
Elucidation of molecular pathogenesis of AFib amyloidosis and therapeutic development
| Project/Area Number |
16K21066
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
Pathological medical chemistry
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| Research Institution | Shinshu University |
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Principal Investigator |
Yoshinaga Tsuneaki 信州大学, 学術研究院医学系(医学部附属病院), 助教 (30770226)
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| Research Collaborator |
Okumura Nobuo 信州大学, 保健学科
Yazaki Masaide 信州大学, 保健学科
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | アミロイドーシス / 腎アミロイドーシス / フィブリノーゲン / 遺伝性アミロイドーシス |
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| Outline of Final Research Achievements |
We performed the analysis of variant protein using a sample of Chinese Hamster Ovary (CHO) cells producing human type fibrinogen into which 4899_4902 delAGTG mutation of FGA gene. We compared the two sample ; culture supernatant and the disrupted cell. in order to detect an abnormal protein, SDS-PAGE was performed after immunoprecipitation in a cell lysate, and the gel was cut out and to mass spectrometry.In the result, the protein generated from the normal Aα chain was detected up to the end of 600, the abnormal Aα chain was around 475, and could not be detected thereafter, and it was found that the produced protein was more unstable and prone to degradation than the normal type.
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| Free Research Field |
神経内科
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| Academic Significance and Societal Importance of the Research Achievements |
本邦初の変異を有するフィブリノーゲン型アミロイドーシスの細胞モデルを用いて、変異蛋白の解析を行った。本変異を有する患者血漿からは異常fibrinogenが検出できなかったことから異常Aα鎖をもつフィブリノーゲンは早期の段階で生体内のプロテアーゼで分解されており、その断片が一部アミロイド構造にいたって腎臓などに沈着すると想定している。本研究結果からはこの変異を有するフィブリノーゲンAα鎖が野生型に比べ、より早期の段階で分解されることが判明した。
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