Studies onIn VivoFunction of Peroxiredoxins in Knockout Mice
Hanyang Medical Reviews
서 론 산소원자를 포함하는 화학적 반응성 분자인 활성산소(reactive oxygen species, ROS)는 생물학적으로 매우 중요한 기능을 지니고 있다. 활성산소가 적당히 증가하면 세포증식과 분화를 촉진하지만 과다하게 증가하면 지질, 단백질 그리고 DNA에 산화 손상을 일으 켜 결국에는 허혈/재관류(ischemia/reperfusion) 손상, 동맥경화 증, 퇴행성신경질환, 암 그리고 알레르기와 같은 수많은 인체질환 을 일으키는 데 관여한다. 그러므로 세포는 활성산소의 항상성 을 유지하려고 superoxide dismutases (SOD1, SOD2, SOD3), glutathione peroxidase, peroxiredoxins (Prxs), glutaredoxin, thioredoxin 그리고 catalase와 같은 각종 항산화효소 생산체계를 갖추고 있다. 활성산소로는 superoxide (O2 -), hydrogen peroxide (H2O2), 그리 고
... xide (H2O2), 그리 고 hydroxyl free radical (HO•)이 있는데, 세포 내 생성된 H2O2는 전사인자, 인지질분해효소, 인산화효소, 탈인산화효소, 이온 통로 와 G protein을 포함하는 다양한 단백질에 영향을 주므로, 독성 이 없는 농도에서 세포 내 전달자로서의 역할을 한다. 세포 내 H2O2 Hanyang Med Rev 2013;33:97-103 http://dx. 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. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.