Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice.
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.
Lee
Tae-Hoon
TH
Laboratory of Development & Differentiation, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Kim
Sun-Uk
SU
Yu
Seong-Lan
SL
Kim
Sue Hee
SH
Park
Do Sim
DS
Moon
Hyung-Bae
HB
Dho
So Hee
SH
Kwon
Ki-Sun
KS
Kwon
Hyun Jeong
HJ
Han
Ying-Hao
YH
Jeong
Sangkyun
S
Kang
Sang Won
SW
Shin
Hee-Sup
HS
Lee
Kyung-Kwang
KK
Rhee
Sue Goo
SG
Yu
Dae-Yeul
DY
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
D001798:Blood Proteins; C516116:Prdx3 protein, mouse; D017382:Reactive Oxygen Species; D004921:Erythropoietin; D006485:Hemosiderin; D010544:Peroxidases; D061105:Peroxiredoxin III; D054464:Peroxiredoxins