title: Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability.
abstract: The pathophysiology of oxidative hemolytic anemia is closely associated with hemoglobin (Hb) stability; however, the mechanism of how Hb maintains its stability under oxidative stress conditions of red blood cells (RBCs) carrying high levels of oxygen is unknown. Here, we investigated the potential role of peroxiredoxin II (Prx II) in preventing Hb aggregation induced by reactive oxygen species (ROS) using Prx II knockout mice and RBCs of patients with hemolytic anemia. Upon oxidative stress, ROS and Heinz body formation were significantly increased in Prx II knockout RBCs compared to wild-type (WT), which ultimately accelerated the accumulation of hemosiderin and heme-oxygenase 1 in the Prx II knock-out livers. In addition, ROS-dependent Hb aggregation was significantly increased in Prx II knockout RBCs. Interestingly, Prx II interacted with Hb in mouse RBCs, and their interaction, in particular, was severely impaired in RBCs of patients with thalassemia (THAL) and sickle cell anemia (SCA). Hb was bound to the decameric structure of Prx II, by which Hb was protected from oxidative stress. These findings suggest that Prx II plays an important role in preventing hemolytic anemia from oxidative stress by binding to Hb as a decameric structure to stabilize it.
authors.affiliation: KRIBB, Daejeon, Republic of Korea.
authors.forename: Ying-Hao
authors.initials: YH
authors.lastname: Han
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Kwon
authors.forename: Dong-Seok
authors.initials: DS
authors.lastname: Lee
authors.forename: Hye-Lin
authors.initials: HL
authors.lastname: Ha
authors.forename: Doo-Sang
authors.initials: DS
authors.lastname: Park
authors.forename: Eui-Jeon
authors.initials: EJ
authors.lastname: Woo
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Lee
authors.forename: Jin-Man
authors.initials: JM
authors.lastname: Kim
authors.forename: Ho-Byoung
authors.initials: HB
authors.lastname: Chae
authors.forename: Sang Yeol
authors.initials: SY
authors.lastname: Lee
authors.forename: Bo Yeon
authors.initials: BY
authors.lastname: Kim
authors.forename: Do Young
authors.initials: DY
authors.lastname: Yoon
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Eitan
authors.initials: E
authors.lastname: Fibach
authors.forename: Dae-Yeul
authors.initials: DY
authors.lastname: Yu
mesh_terms: D000743:Anemia, Hemolytic / Q000201:enzymology* / Q000235:genetics; D000818:Animals; D004912:Erythrocytes / Q000201:enzymology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D006485:Hemosiderin / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D055550:Protein Stability; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D017382:Reactive Oxygen Species; D006485:Hemosiderin; D054464:Peroxiredoxins; D051547:Heme Oxygenase-1