2014 Fiscal Year Final Research Report
Activation of the Nrf2 system in response to endoplasmic reticulum stress
| Project/Area Number |
24590340
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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 |
General medical chemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 小胞体ストレス / Nrf2システム / ゼブラフィッシュ |
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| Outline of Final Research Achievements |
The Aim of this research was to understand physiological roles and molecular mechanism of the Nrf2 activation in response to endoplasmic reticulum stress. We used two zebrafish mutant lines pmm2it768 and nrf2fh318 for this study: pmm2it768 shows spontaneous endoplasmic reticulum stress. We prepared and analyzed pmm2it768;nrf2fh318 double mutants and found that endoplasmic reticulum stress was increased in double mutants compared with pmm2it768 single mutants, indicating that Nrf2 plays significant roles in reducing endoplasmic reticulum stress. Next, we carried out gene-overexpression and -knockdown analyses, and demonstrated that co-overexpression of PERK and ATF4, but not PERK alone, could induce Nrf2 activation. Our results suggest that Nrf2 was activated by the accumulation of ATF4 protein via the PERK pathway, which is a different hypothesis from an existing model.
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| Free Research Field |
分子発生生物学
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