Pathophysiology of sickle cell disease is mirrored by the red blood cell metabolome.
Emerging metabolomic tools can now be used to establish metabolic signatures of specialized circulating hematopoietic cells in physiologic or pathologic conditions and in human hematologic diseases. To determine metabolomes of normal and sickle cell erythrocytes, we used an extraction method of erythrocytes metabolites coupled with a liquid chromatography-mass spectrometry-based metabolite profiling method. Comparison of these 2 metabolomes identified major changes in metabolites produced by (1) endogenous glycolysis characterized by accumulation of many glycolytic intermediates; (2) endogenous glutathione and ascorbate metabolisms characterized by accumulation of ascorbate metabolism intermediates, such as diketogulonic acid and decreased levels of both glutathione and glutathione disulfide; (3) membrane turnover, such as carnitine, or membrane transport characteristics, such as amino acids; and (4) exogenous arginine and NO metabolisms, such as spermine, spermidine, or citrulline. Finally, metabolomic analysis of young and old normal red blood cells indicates metabolites whose levels are directly related to sickle cell disease. These results show the relevance of metabolic profiling for the follow-up of sickle cell patients or other red blood cell diseases and pinpoint the importance of metabolomics to further depict the pathophysiology of human hematologic diseases.
Commissariat à l'Energie Atomique/Direction du Sciences et du vivant/Institut de radiobiologie cellulaire et moléculaire/Laboratoire de Recherche sur la Réparation et la Transcription dans les Cellules Souches, Fontenay-aux-Roses, France.
Dhouha
D
Darghouth
Bérengère
B
Koehl
Geoffrey
G
Madalinski
Jean-François
JF
Heilier
Petra
P
Bovee
Ying
Y
Xu
Marie-Françoise
MF
Olivier
Pablo
P
Bartolucci
Malika
M
Benkerrou
Serge
S
Pissard
Yves
Y
Colin
Frederic
F
Galacteros
Giel
G
Bosman
Christophe
C
Junot
Paul-Henri
PH
Roméo
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000503:physiopathology*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D008954:Models, Biological; D018384:Oxidative Stress; D021241:Spectrometry, Mass, Electrospray Ionization; D055815:Young Adult