2006 Fiscal Year Final Research Report Summary
Role of oxidative stress and the JNK pathway in diabetes
| Project/Area Number |
17390263
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Osaka University |
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Principal Investigator |
MATSUHISA Munehide Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (60362737)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Takaaki Osaka University, Graduate School of Medicine, Specially Appointed Assistant, 医学系研究科, 特任助手 (10379258)
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| Project Period (FY) |
2005 – 2006
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| Keywords | diabetes / pancreatic beta-cells / oxidative stress / JNK pathway / PDX-1 / insulin / Foxol / Rho-kinase |
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| Research Abstract |
It has been shown that oxidative stress and activation of the c-Jun N-terminal kinase (JNK) pathway induce the nucleo-cytoplasmic translocation of the pancreatic transcription factor PDX-1, which leads to pancreatic β-cell dysfunction. In this study, we show that the forkhead transcription factor Foxol/FKHR plays a role as a mediator between the JNK pathway and PDX-1. Under oxidative stress conditions, Foxol changed its intracellular localization from the cytoplasm to the nucleus in the pancreatic β-cell line HIT-T15. The overexpression of JNK also induced the nuclear localization of Foxol, but in contrast, suppression of JNK reduced the oxidative stress-induced nuclear localization of Foxol, suggesting the involvement of the JNK pathway in Foxol translocation. In addition, oxidative stress or activation of the JNK pathway decreased the activity of Akt in HIT cells, leading to the decreased phosphorylation of Foxol following the nuclear localization of Foxol. Furthermore, adenovirus-mediated Foxol overexpression reduced the nuclear expression of PDX-1, whereas repression of Foxol by Foxol-specific siRNA retained the nuclear expression of PDX-1 under oxidative stress conditions. Taken together, Foxol is involved in the nucleo-cytoplasmic translocation of PDX-1 by oxidative stress and the JNK pathway.
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Research Products
(4 results)
