title: The impact of erythrocyte age on eryptosis.
abstract: Mature, circulating erythrocytes undergo senescence, which limits their life span to approximately 120 d. Upon injury, erythrocytes may undergo suicidal erythrocyte death or eryptosis, which may accelerate senescence and shorten their survival. Eryptosis is defined as cell shrinkage and exposure of phosphatidylserine at the cell surface. Triggers of eryptosis include oxidative stress. The present study addresses the impact of erythrocyte age on the relative susceptibility to eryptosis. Erythrocytes were separated into five fractions, based on age-associated differences in density and volume. Cell membrane scrambling was estimated from binding of annexin V to phosphatidylserine at the erythrocyte surface, the cell volume from forward scatter, and the Ca(2+) level from Fluo-3-dependent fluorescence. In addition, glutathione (GSH) concentrations were measured by an enzymatic/colourimetric method. After 48 h incubation in Ringer solution, Annexin V binding increased significantly with erythrocyte age. The differences were not accompanied by altered GSH concentrations, but were reversed by addition of the antioxidant N-acetyl-L-cysteine in vitro. Also, N-acetyl-L-cysteine significantly prolonged the half-life of circulating mouse erythrocytes in vivo. Thus, the susceptibility to eryptosis increases with the age of the erythrocytes, and this effect is at least partially due to enhanced sensitivity to oxidative stress.
authors.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Ghashghaeinia
authors.forename: Judith C A
authors.initials: JC
authors.lastname: Cluitmans
authors.forename: Ahmed
authors.initials: A
authors.lastname: Akel
authors.forename: Peter
authors.initials: P
authors.lastname: Dreischer
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Toulany
authors.forename: Martin
authors.initials: M
authors.lastname: Köberle
authors.forename: Yuliya
authors.initials: Y
authors.lastname: Skabytska
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saki
authors.forename: Tilo
authors.initials: T
authors.lastname: Biedermann
authors.forename: Michael
authors.initials: M
authors.lastname: Duszenko
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Giel J C G M
authors.initials: GJ
authors.lastname: Bosman
mesh_terms: D000111:Acetylcysteine / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism
chemical_list: D010718:Phosphatidylserines; D005978:Glutathione; D002118:Calcium; D000111:Acetylcysteine