Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice
Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice
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DOI：
10.1182/blood-2002-08-2548
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发表时间：
2003-06-15
期刊：
影响因子：
20.3
通讯作者：
Yu, DY
中科院分区：
文献类型：
--
作者：
Lee, TH;Kim, SU;Yu, DY
过氧化物氧还蛋白（Peroxiredoxins，Prxs）是一个抗氧化蛋白家族，通过使用还原剂如硫氧还蛋白降低过氧化物水平。这些蛋白质被表征为具有许多细胞功能，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，我们产生了Prx II缺陷的小鼠模型，其在所有类型的细胞中大量表达。Prx II-/-小鼠外观健康且可生育。然而，他们有脾肿大引起的充血红髓含铁血黄素积累。在他们的外周血中检测到海因茨小体，并且在致密红细胞（RBC）组分中形态异常细胞升高，其中含有显著较高水平的活性氧（ROS）。Prx II-/-小鼠的红细胞压积水平显著降低，但网织红细胞计数和红细胞增多水平升高，表明具有维持小鼠血液稳态的代偿作用。此外，在Prx II-/-小鼠中用巯基修饰试剂生物素化碘乙酰胺（BIAM）进行的标记实验表明，多种RBC蛋白质被高度氧化。我们的结果表明Prx II-/-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发挥着重要作用。(C)2003年，美国血液学会。
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 erythropoletin 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. (C) 2003 by The American Society of Hematology.