title: Enhanced susceptibility to erythrocyte "apoptosis" following phosphate depletion.
abstract: Among the sequelae of phosphate depletion is anaemia, due in part to a decreased life span of mature erythrocytes. Recent studies have disclosed that cellular stress leads to an increase of cytosolic Ca(2+) activity in erythrocytes thereby triggering cell shrinkage and breakdown of phosphatidylserine asymmetry of the cell membrane, both typical features of apoptosis. In the present experiments, phosphatidylserine exposure and cell size were measured by fluorescence-activated cell sorting (FACS) analysis of annexin binding and forward scatter, respectively. Erythrocytes from intact mice were compared with erythrocytes from mice exposed to a low-phosphate diet for 4 days. Annexin binding of freshly drawn erythrocytes was slightly but significantly enhanced by the low-phosphate diet. Furthermore, intracellular phosphate and ATP concentrations were significantly decreased in those erythrocytes whereas intracellular Ca(2+) activity was unaltered. Osmotic shock (exposure to 700 mOsm by addition of sucrose for 12 h), removal of Cl(-) (replaced by gluconate for 15 h) or removal of glucose (12 h) decreased cell volume and increased the number of annexin-binding erythrocytes. Interestingly, these effects were significantly larger in erythrocytes from phosphate-depleted animals. The experiments reveal a novel mechanism triggered by phosphate depletion that presumably contributes to the enhanced vulnerability and accelerated sequestration of erythrocytes and, thus, to anaemia.
authors.affiliation: Physiologisches Institut der Universität Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Birka
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Kempe
authors.forename: Lena
authors.initials: L
authors.lastname: Hoefling
authors.forename: Valerie
authors.initials: V
authors.lastname: Tanneur
authors.forename: Christophe
authors.initials: C
authors.lastname: Duranton
authors.forename: Srinivas
authors.initials: S
authors.lastname: Nammi
authors.forename: Guido
authors.initials: G
authors.lastname: Henke
authors.forename: Svetlana
authors.initials: S
authors.lastname: Myssina
authors.forename: Maxim
authors.initials: M
authors.lastname: Krikov
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000255:Adenosine Triphosphate / Q000032:analysis; D000740:Anemia / Q000503:physiopathology; D000818:Animals; D017302:Annexins / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D048429:Cell Size; D004912:Erythrocytes / Q000737:chemistry / Q000502:physiology*; D005434:Flow Cytometry; D007424:Intracellular Fluid / Q000737:chemistry; D008297:Male; D051379:Mice; D010710:Phosphates / Q000032:analysis / Q000172:deficiency*; D010718:Phosphatidylserines / Q000378:metabolism; D016226:Phosphorus, Dietary
chemical_list: D017302:Annexins; D010710:Phosphates; D010718:Phosphatidylserines; D016226:Phosphorus, Dietary; D000255:Adenosine Triphosphate