2009 Fiscal Year Final Research Report
Role of Peroxiredoxin on Metabolic Syndorome
| Project/Area Number |
19590413
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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 |
Experimental pathology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
SASAGURI Yasuyuki University of Occupational and Environmental Health, Japan, 医学部, 教授 (60140646)
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| Co-Investigator(Kenkyū-buntansha) |
KOHNO Kimitoshi 産業医科大学, 医学部, 教授 (00153479)
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| Project Period (FY) |
2007 – 2009
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| Keywords | 疾患モデル動物 |
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| Research Abstract |
1 We generated human PRDX4 (hPRDX4) transgenic (Tg) mice, displaying a high level of hPRDX4 expression in the pancreatic islets, and then focused on the functions of PRDX4 in a type 1 diabetes mellitus (T1DM) model using a single high dose of streptozotocin (SHDS). After SHDS-injection, Tg mice showed significantly less hyperglycemia and hypoinsulinemia and a much faster response on glucose tolerance test than wild type (WT) mice. Upon comparison between these two mouse models, β-cell apoptosis was also repressed, and reversely, β-cell proliferation was enhanced in Tg mice. Real-time RT-PCR demonstrated that the expression of many inflammatory-related molecules and their receptors and transcription factors were significantly down-regulated in Tg mice. These data indicate that PRDX4 can protect pancreatic islet β-cells against injury caused by SHDS-induced insulitis, which strongly suggests that oxidative stress plays an essential role in SHDS-induced diabetes.
2 To define the role of PRDX4 in atherosclerosis, we generated PRDX4-Tg and apoE knockout mice (hPRDX4-Tg/apoE^<-/-> mice). En-face quantitative and sectinal analysis of aortas demonsurated that atheroscleroosis in hPRDX4-Tg/apoE^<-/-> mice fed a 1.25% cholesterol diet for 12 wk were decreased up-to 40-50% compared with apoE^<-/->. These indicate that PRDX4 may be a suppressive factor for the progression of atherosclerosis.
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[Journal Article] OVEREXPRESSION OF PEROXIREDOXIN4 PROTECTS AGAINST HIGH-DOSE STREPTOZOTOCIN-INDUCED DIABETES BY SUPPRESSING OXIDATIVE STRESS AND CYTOKINES IN TRANSGENIC MICE2010
Author(s)
YAN DING, 1 SOHSUKE YAMADA, 1KE-YONG WANG, 1 SHOHEI SHIMAJIRI, 1 XIN GUO, 1 AKIHIDE TANIMOTO, 2, 1 SHUJI KITAJIMA, 3 TERUO WATANABE, 4 HIROTO IZUMI, 5 KIMITOSHI KOHNO, 5 YASUYUKI SASAGURI1
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Journal Title
Antioxidants & Redox Signaling (in press)
Peer Reviewed
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