Journal
ANTIOXIDANTS & REDOX SIGNALING
Volume 13, Issue 10, Pages 1477-1490Publisher
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2010.3137
Keywords
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology, Tokyo, Japan [19590413, 20590416]
- Grants-in-Aid for Scientific Research [20590416, 19590413, 22500386] Funding Source: KAKEN
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Peroxiredoxin 4 (PRDX4) is one of a newly discovered family of antioxidative proteins. 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. Morphologic and immunohistochemical observation revealed that the pancreatic islet areas of Tg mice were larger along with less CD3-positive lymphocyte infiltration compared with WT mice. Upon comparison between these two mouse models, beta-cell apoptosis was also repressed, and reversely, beta-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 downregulated in Tg mice. These data indicate that PRDX4 can protect pancreatic islet beta-cells against injury caused by SHDS-induced insulitis, which strongly suggests that oxidative stress plays an essential role in SHDS-induced diabetes. This study, for the first time, implicates that PRDX4 has a pivotal protective function against diabetes progression in this T1DM model. Antioxid. Redox Signal. 13, 1477-1490.
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