Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability

Han, Ying‐Hao; Kim, Sun-Uk; Kwon, Taeho; Lee, Dong‐Seok; Ha, Hojin; Park, Doo-Sang; Woo, Eui-Jeon; Lee, Sang‐Hee; Kim, Jin Man; Chae, Ho-Byoung; Lee, Sang Yeol; Kim, Bo Yeon; Yoon, Do Young; Rhee, Sue Goo; Fibach, Eitan; Yu, Dae‐Yeul

doi:10.1016/j.bbrc.2012.08.113

Cited by 61 publications

(41 citation statements)

References 23 publications

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“…With respect to the possible toxic effects of targeting such proteins with essential functions, it is interesting to note that homozygous null Prx2 mice are relatively healthy and fertile. They do however exhibit a mild anemia and splenomegaly, which is exacerbated if the animals are exposed to oxidant stress-inducing compounds [30], [31]. The action of a compound like BBMQ would have an added advantage in this context by virtue of its irreversible action; short-term treatment would be effective for the life of the red cell (since new protein synthesis does not occur), while synthetically active cells, including erythrocyte progenitors, would restore the pool of functional enzyme.…”

Section: Discussionmentioning

confidence: 99%

Treatment of Erythrocytes with the 2-Cys Peroxiredoxin Inhibitor, Conoidin A, Prevents the Growth of Plasmodium falciparum and Enhances Parasite Sensitivity to Chloroquine

et al. 2014

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The human erythrocyte contains an abundance of the thiol-dependant peroxidase Peroxiredoxin-2 (Prx2), which protects the cell from the pro-oxidant environment it encounters during its 120 days of life in the blood stream. In malarial infections, the Plasmodium parasite invades red cells and imports Prx2 during intraerythrocytic development, presumably to supplement in its own degradation of peroxides generated during cell metabolism, especially hemoglobin (Hb) digestion. Here we demonstrate that an irreversible Prx2 inhibitor, Conoidin A (2,3-bis(bromomethyl)-1,4-dioxide-quinoxaline; BBMQ), has potent cytocidal activity against cultured P. falciparum. Parasite growth was also inhibited in red cells that were treated with BBMQ and then washed prior to parasite infection. These cells remained susceptible to merozoite invasion, but failed to support normal intraerythrocytic development. In addition the potency of chloroquine (CQ), an antimalarial drug that prevents the detoxification of Hb-derived heme, was significantly enhanced in the presence of BBMQ. CQ IC50 values decreased an order of magnitude when parasites were either co-incubated with BBMQ, or introduced into BBMQ-pretreated cells; these effects were equivalent for both drug-resistant and drug-sensitive parasite lines. Together these results indicate that treatment of red cells with BBMQ renders them incapable of supporting parasite growth and increases parasite sensitivity to CQ. We also propose that molecules such as BBMQ that target host cell proteins may constitute a novel host-directed therapeutic approach for treating malaria.

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Section: Discussionmentioning

confidence: 99%

Treatment of Erythrocytes with the 2-Cys Peroxiredoxin Inhibitor, Conoidin A, Prevents the Growth of Plasmodium falciparum and Enhances Parasite Sensitivity to Chloroquine

et al. 2014

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“…Despite extensive knowledge of the molecular defects causing thalassemia(s), less is known about the mechanisms responsible for the associated ineffective erythropoiesis (44). Increased levels of ROS have been reported to contribute to the anemia of β thalassemia, however the protective mechanisms against oxidative stress in β thalassemia have not been comprehensively addressed (1,17). these systems limits the ROS generation thereby contributing to cellular resistance and survival against cytotoxic events such as oxidative stress mediated cytotoxic events.…”

Section: Introductionmentioning

confidence: 99%

The Interplay Between Peroxiredoxin-2 and Nuclear Factor-Erythroid 2 Is Important in Limiting Oxidative Mediated Dysfunction in β-Thalassemic Erythropoiesis

Mattè

Falco

Iolascon

et al. 2015

Antioxidants & Redox Signaling

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“…Oxidative stress can induce oxidative PTMs in hemoglobin [26]. PRDX2 bind and stabilize hemoglobin against excessive oxidative stress-induced aggregation [27]. High levels of plasma glucose produce glycated hemoglobin (HbA1C), a marker of diabetes progression, making hemoglobin more amenable to oxidation [28].…”

Section: Discussionmentioning

confidence: 99%

Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parameters

Feliciano

Vaz

Torres

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that atmorning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation.

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Peroxiredoxin II is essential for preventing hemolytic anemia from oxidative stress through maintaining hemoglobin stability

Cited by 61 publications

References 23 publications

Treatment of Erythrocytes with the 2-Cys Peroxiredoxin Inhibitor, Conoidin A, Prevents the Growth of Plasmodium falciparum and Enhances Parasite Sensitivity to Chloroquine

Treatment of Erythrocytes with the 2-Cys Peroxiredoxin Inhibitor, Conoidin A, Prevents the Growth of Plasmodium falciparum and Enhances Parasite Sensitivity to Chloroquine

The Interplay Between Peroxiredoxin-2 and Nuclear Factor-Erythroid 2 Is Important in Limiting Oxidative Mediated Dysfunction in β-Thalassemic Erythropoiesis

Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parameters

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