Lee Tae-Hoon, Kim Sun-Uk, Yu Seong-Lan, Kim Sue Hee, Park Do Sim, Moon Hyung-Bae, Dho So Hee, Kwon Ki-Sun, Kwon Hyun Jeong, Han Ying-Hao, Jeong Sangkyun, Kang Sang Won, Shin Hee-Sup, Lee Kyung-Kwang, Rhee Sue Goo, Yu Dae-Yeul
Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Blood. 2003 Jun 15;101(12):5033-8. doi: 10.1182/blood-2002-08-2548. Epub 2003 Feb 13.
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. However, the physiological roles of the peroxiredoxins have not been determined. To clarify the physiological relevance of this protein type, we generated a mouse model deficient in Prx II, which is abundantly expressed in all types of cells. The Prx II-/- mice were healthy in appearance and fertile. However, they had splenomegaly caused by the congestion of red pulp with hemosiderin accumulation. Heinz bodies were detected in their peripheral blood, and morphologically abnormal cells were elevated in the dense red blood cell (RBC) fractions, which contained markedly higher levels of reactive oxygen species (ROS). The Prx II-/- mice had significantly decreased hematocrit levels, but increased reticulocyte counts and erythropoietin levels, indicative of a compensatory action to maintain hematologic homeostasis in the mice. In addition, a labeling experiment with the thiol-modifying reagent biotinylated iodoacetamide (BIAM) in Prx II-/- mice revealed that a variety of RBC proteins were highly oxidized. Our results suggest that Prx II-/- mice have hemolytic anemia and that Prx II plays a major role in protecting RBCs from oxidative stress in mice.
过氧化物酶（Prxs）是一类抗氧化蛋白，它们通过使用硫氧还蛋白等还原剂来降低过氧化物水平。这些蛋白质具有多种细胞功能，包括细胞增殖和分化以及保护特定蛋白质免受氧化损伤。然而，过氧化物酶的生理作用尚未确定。为了阐明这种蛋白质类型的生理相关性，我们构建了一种Prx II基因缺陷的小鼠模型，Prx II在所有类型的细胞中都大量表达。Prx II基因敲除小鼠外观健康且可育。然而，它们出现了脾肿大，这是由于红髓充血伴含铁血黄素积累所致。在它们的外周血中检测到了海因茨小体，并且在密集的红细胞（RBC）组分中形态异常的细胞增多，这些组分中活性氧（ROS）水平明显更高。Prx II基因敲除小鼠的血细胞比容水平显著降低，但网织红细胞计数和促红细胞生成素水平升高，这表明小鼠体内存在维持血液学稳态的代偿作用。此外，在Prx II基因敲除小鼠中用硫醇修饰试剂生物素化碘乙酰胺（BIAM）进行的标记实验表明，多种红细胞蛋白被高度氧化。我们的结果表明，Prx II基因敲除小鼠患有溶血性贫血，并且Prx II在保护小鼠红细胞免受氧化应激方面起主要作用。
