title: Decreased cation channel activity and blunted channel-dependent eryptosis in neonatal erythrocytes.
abstract: Eryptosis or apoptosis-like death of erythrocytes is characterized by phosphatidylserine exposure and erythrocyte shrinkage, both typical features of nucleated apoptotic cells. Eryptosis is triggered by activation of nonselective Ca(2+)-permeable cation channels with subsequent entry of Ca(2+) and stimulation of Ca(2+)-sensitive scrambling of the cell membrane. The channels are activated and thus eryptosis is triggered by Cl(-) removal, osmotic shock, oxidative stress, or glucose deprivation. The present study has been performed to compare cation channel activity and susceptibility to eryptosis in neonatal and adult erythrocytes. Channel activity was determined by patch-clamp analysis, cytosolic Ca(2+) activity by fluo-3 fluorescence, phosphatidylserine exposure by FITC-labeled annexin V binding, and cell shrinkage by decrease in forward scatter in fluorescence-activated cell sorting analysis. Prostaglandin E(2) (PGE(2)) formation, cation channel activity, Ca(2+) entry, annexin V binding, and decreased forward scatter were triggered by removal of Cl(-) in both adult and neonatal erythrocytes. The effects were, however, significantly blunted in neonatal erythrocytes. Osmotic shock, PGE(2,) and platelet-activating factor similarly increased annexin V binding and decreased forward scatter, effects again significantly reduced in neonatal erythrocytes. On the other hand, spontaneous and oxidative (addition of tert-butylperoxide) stress-induced eryptosis was significantly larger in neonatal erythrocytes. In conclusion, cation channel activity, Ca(2+) leakage, and thus channel-dependent triggering of eryptosis are blunted, whereas spontaneous and oxidative stress-induced eryptosis is more pronounced in neonatal erythrocytes.
authors.affiliation: Department of Physiology, University of Tübingen, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Hermle
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Philipp
authors.initials: P
authors.lastname: Attanasio
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akel
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Kempe
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Marlies
authors.initials: M
authors.lastname: Podolski
authors.forename: Sabine
authors.initials: S
authors.lastname: Gatz
authors.forename: Robert
authors.initials: R
authors.lastname: Bachmann
authors.forename: Cornelia
authors.initials: C
authors.lastname: Bachmann
authors.forename: Harald
authors.initials: H
authors.lastname: Abele
authors.forename: Stephan
authors.initials: S
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000328:Adult; D000375:Aging / Q000097:blood; D000814:Aniline Compounds; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002412:Cations / Q000378:metabolism*; D002469:Cell Separation; D002712:Chlorides / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology*; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000502:physiology; D018408:Patch-Clamp Techniques; D010718:Phosphatidylserines / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology; D014966:Xanthenes; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D017304:Annexin A5; D002412:Cations; D002712:Chlorides; D005456:Fluorescent Dyes; D007473:Ion Channels; D010718:Phosphatidylserines; D010972:Platelet Activating Factor; D014966:Xanthenes; C059715:Fluo-3; D020122:tert-Butylhydroperoxide; D016650:Fluorescein-5-isothiocyanate; D015232:Dinoprostone; D002118:Calcium