| Project/Area Number |
16K01827
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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 |
Applied health science
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| Research Institution | Saitama University (2018-2019)
Nagoya City University (2016-2017) |
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Principal Investigator |
Nishio Naomi 埼玉大学, 教育学部, 准教授 (80513457)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | GADD34 / インスリンシグナル伝達系 / 老化 / Insulin/IGF1レセプターシグナル伝達 / 肝臓 / Insulin/IGF1レセプターシグナル伝達系 / 脂質合成 / シグナル伝達 / 代謝 / 脂質 / 糖 |
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| Outline of Final Research Achievements |
Previously, we found that mice deficient in DNA damage- inducible protein 34 (GADD34) become obese with age, developing fatty liver followed by liver cirrhosis hepatocellular carcinoma, and insulin resistance. Here, we examined the mechanism underlying the effects of GADD34 on fatty liver disease as age related disease. We found the GADD34 suppressed phosphorylation of the insulin receptor. The higher level of insulin signaling observed in GADD34-deficient liver and mouse embryonic fibroblasts led to accumulation of triglycerides via production of fatty acids. In addition, cellular senescence also accelerated. Then, the level of insulin signaling were decreased in GADD34 deficient liver and MEFs with aging or cellular senescence. Furthermore, we found the expression of Caveolin and Cavin1 on cell membranes were different by deficiency of GADD34. GADD34 may regulate the signal transduction in connection with structure of cell membrane.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、GADD34は小胞体ストレス時の機能が主に報告されてきたが、本研究で、小胞体ストレスのみでなく、細胞膜に刺激が入った時、細胞膜あるいはその近くで作用し、各受容体からのシグナル伝達系を制御することで、老化に伴う細胞構造や代謝の変化に影響し、細胞老化や個体老化を制御している可能性が明らかとなった。このことから、GADD34の老化抑制メカニズムが、今後、老化や老化関連疾患発症の予防や治療を行うための新たな知見となる。
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