title: Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice.
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. 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.
authors.affiliation: Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Seong-Lan
authors.initials: SL
authors.lastname: Yu
authors.forename: Sue Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Do Sim
authors.initials: DS
authors.lastname: Park
authors.forename: Hyung-Bae
authors.initials: HB
authors.lastname: Moon
authors.forename: So Hee
authors.initials: SH
authors.lastname: Dho
authors.forename: Ki-Sun
authors.initials: KS
authors.lastname: Kwon
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Han
authors.forename: Sangkyun
authors.initials: S
authors.lastname: Jeong
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Hee-Sup
authors.initials: HS
authors.lastname: Shin
authors.forename: Kyung-Kwang
authors.initials: KK
authors.lastname: Lee
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
mesh_terms: D000743:Anemia, Hemolytic / Q000209:etiology; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000378:metabolism / Q000648:ultrastructure; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood; D006366:Heinz Bodies; D006400:Hematocrit; D006485:Hemosiderin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D010544:Peroxidases / Q000172:deficiency / Q000502:physiology*; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D017382:Reactive Oxygen Species / Q000097:blood; D017701:Reticulocyte Count; D013163:Splenomegaly
chemical_list: D001798:Blood Proteins; C516116:Prdx3 protein, mouse; D017382:Reactive Oxygen Species; D004921:Erythropoietin; D006485:Hemosiderin; D010544:Peroxidases; D061105:Peroxiredoxin III; D054464:Peroxiredoxins