Overexpression of peroxiredoxin 4 protects against high-dose streptozotocin-induced diabetes by suppressing oxidative stress and cytokines in transgenic mice.
ABSTRACT 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, 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 downregulated 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. This study, for the first time, implicates that PRDX4 has a pivotal protective function against diabetes progression in this T1DM model.
Article: Thioredoxins, glutaredoxins, and peroxiredoxins - molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling.[show abstract] [hide abstract]
ABSTRACT: Thioredoxins, glutaredoxins, and peroxiredoxins have been characterized as electron donors, guards of the intracellular redox state, and 'antioxidants'. Today, these redoxins are increasingly recognized for their specific role in redox signaling. Redoxin research is by no means 'old-fashioned'; on the contrary, the number of publications on the topic continues to increase exponentially. This review summarizes the almost 50 years of redoxin research, focusing primarily on recent data from vertebrates and mammals. The role of Trx family and related proteins in redox signaling is discussed by looking at reaction mechanisms, reversible oxidative post-translational modifications of proteins, and characterized interaction partners of the redoxins. On basis of this analysis, the importance of the redoxins for human health is addressed in the second part of this review, i.e. their potential impact and functions in different cell types, metabolic and signaling pathways, and various pathological conditions.Antioxidants and Redox Signaling 02/2013; · 8.46 Impact Factor