Studies on In Vivo Function of Peroxiredoxins in Knockout Mice / 한양의대학술지

ABSTRACT

Peroxiredoxins (Prxs) are a family of antioxidant proteins that reduce peroxide levels by using reducing agents such as thioredoxin. These proteins were characterized to have a number of cellular functions, including cell proliferation and differentiation and protection of specific proteins from oxidative damage. Thus, it is important to clarify the physiological role of Prxs by generating mouse models deficient in each Prx to better understand the in vivo function of Prxs. We have generated and characterized mice deficient in Prx I and II that are abundantly expressed in almost all types of cells. The Prx II-/- mice were healthy in appearance and fertile, however showed several pathophysiological disorders. Using the mice, we found that Prx II is an essential antioxidant enzyme that prevents oxidative stress in erythropoiesis, protects against endotoxin-induced lethal shock, regulates platelet-derived growth factor signaling and angiogenesis, inhibits cellular senescence, preserves cognitive function against age-linked hippocampal oxidative damage and exacerbates tumorigenesis in a liver cancer mouse model. The Prx I-/- mice were also healthy in appearance and fertile like Prx II-/- mice. With the mice, we found that Prx I suppresses K-ras-driven lung tumorigenesis by opposing the redox-sensitive extracellular-signal-regulated kinase/cyclin D1 pathway and plays concerted action with sulfiredoxin in preventing against alcohol-induced oxidative injury in the mouse liver. The results obtained suggest that Prx I and II are essential antioxidant enzymes for maintaining redox homeostasis in mice.