2016 Fiscal Year Final Research Report
Regulation of unfolded protein response by oxidative stress
Project/Area Number |
15K14952
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Biological pharmacy
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Research Institution | Okayama University |
Principal Investigator |
Uehara Takashi 岡山大学, 医歯薬学総合研究科, 教授 (00261321)
|
Project Period (FY) |
2015-04-01 – 2017-03-31
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Keywords | 一酸化窒素 / 小胞体ストレス / 親電子性物質 / 酸化 / ニトロシル化 / 細胞死 |
Outline of Final Research Achievements |
S-nitrosylation modulates important cellular processes in many cell types. We attempted to elucidate the effects of S-nitrosylation on unfolded protein response (UPR) pathway. We found that nitric oxide (NO) can S-nitrosylate the ER stress sensors IRE1α and PERK. However S-nitrosylation of IRE1α inhibited its ribonuclease activity, S-nitrosylation of PERK activated its kinase activity and downstream phosphorylation/inactivation or eIF2α. Overexpression of IRE1α(Cys931) prevented S-nitrosylation and inhibition of its enzymatic activity, indicating Cys931 is the predominant site of S-nitrosylation. These results indicated that nitrosative stress leads to dysfunctional ER stress signaling, thus contributing to neuronal cell death.
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Free Research Field |
薬理学
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