title: PGE(2) in the regulation of programmed erythrocyte death.
abstract: Hyperosmotic shock, energy depletion, or removal of extracellular Cl(-) activates Ca(2+)-permeable cation channels in erythrocyte membranes. Subsequent Ca(2+) entry induces erythrocyte shrinkage and exposure of phosphatidylserine (PS) at the erythrocyte surface. PS-exposing cells are engulfed by macrophages. The present study explored the signalling involved. Hyperosmotic shock and Cl(-) removal triggered the release of prostaglandin E(2) (PGE(2)). In whole-cell recording, activation of the cation channels by Cl(-) removal was abolished by the cyclooxygenase inhibitor diclophenac. In FACS analysis, phospholipase-A(2) inhibitors quinacrine and palmitoyltrifluoromethyl-ketone, and cyclooxygenase inhibitors acetylsalicylic acid and diclophenac, blunted the increase of PS exposure following Cl(-) removal. PGE(2) (but not thromboxane) induced cation channel activation, increase in cytosolic Ca(2+) concentration, cell shrinkage, PS exposure, calpain activation, and ankyrin-R degradation. The latter was attenuated by calpain inhibitors-I/II, while PGE(2)-induced PS exposure was not. In conclusion, hyperosmotic shock or Cl(-) removal stimulates erythrocyte PS exposure through PGE(2) formation and subsequent activation of Ca(2+)-permeable cation channels.
authors.affiliation: Department of Physiology, University of Tübingen, Germany. florian.lang@uni-tuebingen.de
authors.forename: P A
authors.initials: PA
authors.lastname: Lang
authors.forename: D S
authors.initials: DS
authors.lastname: Kempe
authors.forename: S
authors.initials: S
authors.lastname: Myssina
authors.forename: V
authors.initials: V
authors.lastname: Tanneur
authors.forename: C
authors.initials: C
authors.lastname: Birka
authors.forename: S
authors.initials: S
authors.lastname: Laufer
authors.forename: F
authors.initials: F
authors.lastname: Lang
authors.forename: T
authors.initials: T
authors.lastname: Wieder
authors.forename: S M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D017487:Ankyrins / Q000378:metabolism; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects; D002154:Calpain / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008954:Models, Biological; D009997:Osmotic Pressure / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010718:Phosphatidylserines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism* / Q000494:pharmacology; D011796:Quinacrine / Q000494:pharmacology; D012462:Saline Solution, Hypertonic
chemical_list: D017487:Ankyrins; D017302:Annexins; D015220:Calcium Channels; D002712:Chlorides; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D011458:Prostaglandins E; D012462:Saline Solution, Hypertonic; D004008:Diclofenac; D010741:Phospholipases A; D002154:Calpain; D011796:Quinacrine; D002118:Calcium