Changes in red blood cell membrane structure in G6PD deficiency: an atomic force microscopy study.
BACKGROUND
Glucose-6-phosphate dehydrogenase deficiency affects over 400 million people worldwide. The hemolytic anemia in G6PD deficiency is usually triggered by oxidative stress, but the mechanism remains uncertain. We have used atomic force microscopy for studying changes in red blood cell membrane and providing new insights on the mechanism.


METHODS
G6PD activity assay and molecular genetic tests were used for molecular diagnosis. AFM was used to investigate alterations in the ultrastructure of G6PD deficient RBC membranes, the influence of different primaquine concentrations, and the protective effects of vitamin C.


RESULTS
Nine variants were identified from 33 G6PD deficient individuals. AFM imaging and quantitative analysis showed that G6PD deficient erythrocytes became heterogeneous and roughness measurements of erythrocyte membranes are increased. G6PD enzyme activity and different mutations may relate with roughness parameters. Furthermore, primaquine induces an increased roughness and height of erythrocyte membrane. Meanwhile, primaquine induces damages to erythrocytes which could be prevented by vitamin C treatment in normal RBCs but not in G6PD deficient erythrocytes.


CONCLUSIONS
Our research may give valuable information about the status of G6PD deficient patients and explore the mechanism of hemolytic anemia.
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Jia
J
Tang
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Chengrui
C
Jiang
Department of Clinical Laboratory Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
Xiao
X
Xiao
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Zishui
Z
Fang
Department of Clinical Laboratory Medicine, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510000, China.
Lei
L
Li
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Luhao
L
Han
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Anqi
A
Mei
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Yi
Y
Feng
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Yibin
Y
Guo
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
Hongyi
H
Li
Department of Medical Genetics, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China; University and Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou 510080, China. Electronic address: jiangwy@mail.sysu.edu.cn.
Weiying
W
Jiang
D001205:Ascorbic Acid / Q000494:pharmacology; D021961:Cell Membrane Structures / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D005838:Genotype; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood* / Q000473:pathology; D006801:Humans; D018625:Microscopy, Atomic Force; D011319:Primaquine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D011319:Primaquine; D001205:Ascorbic Acid
AFM; G6PD deficiency; Primaquine; RBCs membrane; Vitamin C