2012 Fiscal Year Final Research Report
Regulation of ER stress response by insulin signaling
| Project/Area Number |
22590553
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hygiene
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
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| Project Period (FY) |
2010 – 2012
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| Keywords | インスリン / 小胞体ストレス / GRP78/Bip / ATF4 / アポトーシス / 神経保護 |
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| Research Abstract |
The effect of insulin on endoplasmic reticulum (ER) stress was investigated. Insulin protected cell death induced by ER stress and increased glucose-regulated protein 78 (GRP78) mRNA and protein levels. Insulin also significantly increased activating transcription factor-4 (ATF4) protein level through PI-3 kinase/AKT pathway. The increase of ATF4 protein by insulin was not due to transcriptional or transational up-regulation but to a post-translational mechanism. Knockdown of ATF4 by siRNA significantly inhibited GRP78 induction by insulin. These results indicate that insulin modulated ER stress-induced GRP78 expression occurs via ATF4 up-regulation.
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