Peroxiredoxin 4 (PRDX4): Its critical in vivo roles in animal models of metabolic syndrome ranging from atherosclerosis to nonalcoholic fatty liver disease

• Published in: Pathology international 2018-02, Vol.68 (2), p.91-101
• Main Authors: Yamada, Sohsuke, Guo, Xin
• Format: Article
• Language: English
• Subjects: Accelerators; animal model; Animal models; Animals; Apoptosis; Arteriosclerosis; Atherosclerosis; Atherosclerosis - metabolism; Chemical compounds; chronic inflammatory disease; Diabetes mellitus; Disease Models, Animal; Endoplasmic reticulum; Fatty liver; Glucose metabolism; human PRDX4 transgenic mice (Tg); Humans; Inflammation - metabolism; Inflammatory diseases; Insulin; Intestine; Intracellular; Lipid metabolism; Liver; Liver - metabolism; Liver diseases; Localization; Metabolic syndrome; Metabolic Syndrome - metabolism; Metabolism; Mice; Non-alcoholic Fatty Liver Disease - metabolism; Oxidative stress; Oxidative Stress - physiology; Peroxiredoxin; peroxiredoxin (PRDX) 4; Peroxiredoxins - metabolism; Pharmacology; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Rodents; Steatosis; Transgenic mice
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/pin.12634

The peroxiredoxin (PRDX) family, a new family of proteins with a pivotal antioxidative function, is ubiquitously synthesized and abundantly identified in various organisms. In contrast to the intracellular localization of other family members (PRDX1/2/3/5/6), PRDX4 is the only known secretory form and protects against oxidative damage by scavenging reactive oxygen species in both the intracellular (especially the endoplasmic reticulum) compartments and the extracellular space. We generated unique human PRDX4 (hPRDX4) transgenic (Tg) mice on a C57BL/6J background and investigated the critical and diverse protective roles of PRDX4 against diabetes mellitus, atherosclerosis, insulin resistance, and nonalcoholic fatty liver disease (NAFLD) as well as evaluated its role in the intestinal function in various animal models. Our published data have shown that PRDX4 helps prevent the progression of metabolic syndrome by reducing local and systemic oxidative stress and synergistically suppressing steatosis, inflammatory reactions, and/or apoptotic activity. These observations suggest that Tg mice may be a useful animal model for studying the relevance of oxidative stress on inflammation and the dysregulation of lipid/bile acid/glucose metabolism upon the progression of human metabolic syndrome, and that specific accelerators of PRDX4 may be useful as therapeutic agents for ameliorating various chronic inflammatory diseases.