title: Red blood cell aquaporin-1 expression is decreased in hereditary spherocytosis.
abstract: Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes.
authors.affiliation: División Hematología Clínica, Departamento de Medicina, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina.|Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|Consultorios de Hematología Infantil, Buenos Aires, Argentina.
authors.forename: Renée L
authors.initials: RL
authors.lastname: Crisp
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Pabellón II, Piso 4, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires, C1428EHA, Argentina.
authors.forename: Romina E
authors.initials: RE
authors.lastname: Maltaneri
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.|IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Pabellón II, Piso 4, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires, C1428EHA, Argentina.
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Vittori
authors.affiliation: Laboratorio de Citometría, Departamento de Diagnóstico, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina.
authors.forename: Liliana
authors.initials: L
authors.lastname: Solari
authors.affiliation: Laboratorio de Citometría, Departamento de Diagnóstico, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Gammella
authors.affiliation: Consultorios de Hematología Infantil, Buenos Aires, Argentina.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Schvartzman
authors.affiliation: Servicio de Oncohematología Pediátrica, Departamento de Pediatría, Hospital Nacional Alejandro Posadas, Buenos Aires, Argentina.
authors.forename: Eliana
authors.initials: E
authors.lastname: García
authors.affiliation: Sección Hematología/Oncología, Hospital Municipal del Niño de San Justo, San Justo, Buenos Aires, Argentina.
authors.forename: María C
authors.initials: MC
authors.lastname: Rapetti
authors.affiliation: Consultorios de Hematología Infantil, Buenos Aires, Argentina.|Sección Hematología/Oncología, Hospital Municipal del Niño de San Justo, San Justo, Buenos Aires, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Donato
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. anesse@qb.fcen.uba.ar.|IQUIBICEN-CONICET (Consejo Nacional de Investigaciones Científicas y Técnicas), Pabellón II, Piso 4, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires, C1428EHA, Argentina. anesse@qb.fcen.uba.ar.
authors.forename: Alcira
authors.initials: A
authors.lastname: Nesse
mesh_terms: D000293:Adolescent; D000328:Adult; D000744:Anemia, Hemolytic, Autoimmune / Q000097:blood / Q000235:genetics; D051398:Aquaporin 1 / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D001692:Biological Transport; D001834:Body Water; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D004921:Erythropoietin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006461:Hemolysis; D006579:Heterozygote; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood; D008875:Middle Aged; D009994:Osmolar Concentration; D009996:Osmotic Fragility; D013103:Spherocytosis, Hereditary / Q000097:blood* / Q000235:genetics / Q000601:surgery; D013156:Splenectomy
chemical_list: D004921:Erythropoietin; D051398:Aquaporin 1
keywords: Aquaporin-1; Erythropoietin; Serum osmolality; Spherocytosis