title: Enhanced erythrocyte apoptosis in sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency.
abstract: Erythrocyte diseases such as sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency decrease the erythrocyte life span, an effect contributing to anemia. Most recently, erythro-cytes have been shown to undergo apoptosis upon increase of cytosolic Ca(2+) activity. The present study has been performed to explore whether sickle cell anemia, thalassemia and glucose-6-phosphate dehydrogenase deficiency enhance the sensitivity of erythrocytes to osmotic shock, oxidative stress or energy depletion, all maneuvers known to increase cytosolic Ca(2+) activity. To this end, annexin binding as an indicator of apoptosis has been determined by FACS analysis. Erythrocytes from healthy individuals, from patients with sickle cell anemia, thalassemia or glucose-6-phosphate dehydrogenase deficiency all responded to osmotic shock (up to 950 mOsm by addition of sucrose for 24 hours), to oxidative stress (up to 1.0 mM tetra-butyl-hydroxyperoxide tBOOH) and to energy depletion (up to 48 hours glucose deprivation) with enhanced annexin binding. However, the sensitivity of sickle cells and of glucose-6-phosphate dehydrogenase deficient cells to osmotic shock and of sickle cells, thalassemic cells and glucose-6-phosphate dehydrogenase deficient cells to oxidative stress and to glucose depletion was significantly higher than that of control cells. Annexin binding was further stimulated by Ca(2+) ionophore ionomycin with significantly higher sensitivity of sickle cells and glucose-6-phosphate dehydrogenase deficient cells as compared to intact cells. In conclusion, sickle cells, thalassemic cells and glucose-6-phosphate dehydrogenase deficient erythrocytes are more sensitive to osmotic shock, oxidative stress and/or energy depletion, thus leading to enhanced apoptosis of those cells. The accelerated apoptosis then contributes to the shortened life span of the defective erythrocytes.
authors.affiliation: Department of Physiology, University of Tuebingen, Germany.
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Roll
authors.forename: Svetlana
authors.initials: S
authors.lastname: Myssina
authors.forename: Markus
authors.initials: M
authors.lastname: Schittenhelm
authors.forename: Hans-Gerhard
authors.initials: HG
authors.lastname: Scheel-Walter
authors.forename: Lothar
authors.initials: L
authors.lastname: Kanz
authors.forename: Jasmin
authors.initials: J
authors.lastname: Fritz
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
mesh_terms: D000704:Analysis of Variance; D000755:Anemia, Sickle Cell / Q000097:blood*; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D016001:Confidence Intervals; D004910:Erythrocyte Membrane / Q000378:metabolism; D004913:Erythrocytes, Abnormal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D005947:Glucose / Q000172:deficiency; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000097:blood*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000502:physiology; D010718:Phosphatidylserines / Q000097:blood; D013789:Thalassemia / Q000097:blood*
chemical_list: D017302:Annexins; D010718:Phosphatidylserines; D015759:Ionomycin; D006861:Hydrogen Peroxide; D005947:Glucose