title: Proteomic analysis of hemoglobin H-constant spring (Hb H-CS) erythroblasts.
abstract: Hemoglobin H disease (Hb H) arises through the loss or dysfunction of three of the four alpha globin genes through the co-inheritance of either gross gene deletions or an abnormal hemoglobin which causes a non-deletional loss of α-globin expression. This study sought to investigate erythropoiesis in Hb H-Constant Spring (Hb H-CS) disease, a common form of Hb H disease in Southeast Asia, caused by the inheritance of the Constant Spring variant hemoglobin together with deletion of two of the alpha globin genes. In comparison to normal erythroblasts, Hb H-CS erythroblasts showed reduced cell expansion although no difference in differentiation was observed. Proteomic analysis revealed the increased expression of both chaperone and chaperonin proteins as well as down regulation of proteins regulating apoptosis. Both chaperone and chaperonin mediated folding require ATP, and evidence of increase energy demand was seen in the form of increased expression of enzymes involved in purine biosynthesis and increased levels of reactive oxygen species. A significant increase in apoptosis was seen in Hb H-CS erythroblasts, and the results from the proteomic analysis suggest that this arises at least in part from the consequences of increased folding requirements in the Hb H-CS erythroblast.
authors.affiliation: Molecular Pathology Laboratory, Institute of Molecular Biosciences, Mahidol University, Thailand.
authors.forename: Sukanya
authors.initials: S
authors.lastname: Sriiam
authors.forename: Amporn
authors.initials: A
authors.lastname: Leecharoenkiat
authors.forename: Pathrapol
authors.initials: P
authors.lastname: Lithanatudom
authors.forename: Tirawat
authors.initials: T
authors.lastname: Wannatung
authors.forename: Saovaros
authors.initials: S
authors.lastname: Svasti
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Jisnuson
authors.initials: J
authors.lastname: Svasti
authors.forename: Daranee
authors.initials: D
authors.lastname: Chokchaichamnankit
authors.forename: Chantragan
authors.initials: C
authors.lastname: Srisomsap
authors.forename: Duncan R
authors.initials: DR
authors.lastname: Smith
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D017209:Apoptosis; D002454:Cell Differentiation; D004900:Erythroblasts / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D008297:Male; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D018952:Antigens, CD34; D006455:Hemoglobins, Abnormal; D020543:Proteome; D017382:Reactive Oxygen Species; C035541:Hemoglobin Constant Spring