New insights provided by a comparison of impaired deformability with erythrocyte oxidative stress for sickle cell disease.
Sickle cell disease (SCD) is associated with increase in oxidative stress and irreversible membrane changes that originates from the instability and polymerization of deoxygenated hemoglobin S (HbS). The relationship between erythrocyte membrane changes as assessed by a decrease in deformability and oxidative stress as assessed by an increase in heme degradation was investigated. The erythrocyte deformability and heme degradation for 27 subjects with SCD and 7 with sickle trait were compared with normal healthy adults. Changes in both deformability and heme degradation increased in the order of control to trait to non-crisis SCD to crisis SCD resulting in a very significantly negative correlation between deformability and heme degradation. However, a quantitative analysis of the changes in deformability and heme degradation for these different groups of subjects indicated that sickle trait had a much smaller effect on deformability than on heme degradation, while crisis affects deformability to a greater extent than heme degradation. These findings provide insights into the relative contributions of erythrocyte oxidative stress and membrane damage during the progression of SCD providing a better understanding of the pathophysiology of SCD.
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Viachaslau M
VM
Barodka
Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
Enika
E
Nagababu
Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
Joy G
JG
Mohanty
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Daniel
D
Nyhan
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
Dan E
DE
Berkowitz
Molecular Dynamics Section, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States. Electronic address: rifkindj@mail.nih.gov.
Joseph M
JM
Rifkind
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
John J
JJ
Strouse
D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology*; D004913:Erythrocytes, Abnormal / Q000378:metabolism*; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D059748:Proteolysis; D012805:Sickle Cell Trait / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D006451:Hemoglobin, Sickle; D006454:Hemoglobins; D006418:Heme; D005319:Fetal Hemoglobin
Deformability; Erythrocytes; Fluorescence; Heme degradation; Hemoglobin; Sickle cell disease