Reduced oxidative-stress response in red blood cells from p45NFE2-deficient mice.
p45NF-E2 is a member of the cap 'n' collar (CNC)-basic leucine zipper family of transcriptional activators that is expressed at high levels in various types of blood cells. Mice deficient in p45NF-E2 that were generated by gene targeting have high mortality from bleeding resulting from severe thrombocytopenia. Surviving p45nf-e2(-/-) adults have mild anemia characterized by hypochromic red blood cells (RBCs), reticulocytosis, and splenomegaly. Erythroid abnormalities in p45nf-e2(-/-) animals were previously attributed to stress erythropoiesis caused by chronic bleeding and, possibly, ineffective erythropoiesis. Previous studies suggested that CNC factors might play essential roles in regulating expression of genes that protect cells against oxidative stress. In this study, we found that p45NF-E2-deficient RBCs have increased levels of reactive oxygen species and an increased susceptibility to oxidative-stress-induced damage. Deformability of p45NF-E2-deficient RBCs was markedly reduced with oxidative stress, and mutant cells had a reduced life span. One possible reason for increased sensitivity to oxidative stress is that catalase levels were reduced in mutant RBCs. These findings suggest a role for p45NF-E2 in the oxidative-stress response in RBCs and indicate that p45NF-E2 deficiency contributes to the anemia in p45nf-e2(-/-) mice. (Blood. 2001;97:2151-2158)
Department of Laboratory Medicine, University of California, San Francisco 94143-0793, USA. jchan@socrates.ucsf.edu
J Y
JY
Chan
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M
Kwong
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M
Lo
R
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Emerson
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Kuypers
D000747:Anemia, Hypochromic / Q000097:blood* / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D004790:Enzyme Induction; D004905:Erythrocyte Aging / Q000235:genetics; D004907:Erythrocyte Deformability; D004913:Erythrocytes, Abnormal / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006474:Hemorrhagic Disorders / Q000235:genetics; D016350:Leucine Zippers / Q000235:genetics* / Q000502:physiology; D008706:Methemoglobin / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009996:Osmotic Fragility; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D010659:Phenylhydrazines / Q000633:toxicity; D017382:Reactive Oxygen Species; D017701:Reticulocyte Count; D013163:Splenomegaly / Q000235:genetics; D013921:Thrombocytopenia / Q000235:genetics; D014157:Transcription Factors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D010659:Phenylhydrazines; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C030299:phenylhydrazine; D008706:Methemoglobin; D002374:Catalase