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Enhanced programmed cell death of iron‐deficient erythrocytes
Author(s) -
Kempe Daniela S.,
Lang Philipp A.,
Duranton Christophe,
Akel Ahmad,
Lang Karl S.,
Huber Stephan M.,
Wieder Thomas,
Lang Florian
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4872fje
Subject(s) - phosphatidylserine , cytosol , annexin , chemistry , oxidative stress , apoptosis , red blood cell , osmotic shock , iron deficiency , programmed cell death , biophysics , reactive oxygen species , microbiology and biotechnology , biochemistry , anemia , biology , medicine , membrane , phospholipid , gene , enzyme
Exposure of erythrocytes to osmotic shock, oxidative stress, and energy depletion activates Cl – sensitive and Ca 2+ ‐permeable cation channels. Subsequent Ca 2+ entry triggers eryptosis, characterized by erythrocyte shrinkage, membrane blebbing, and phosphatidylserine exposure all features typical for apoptotic death of nucleated cells. Erythrocytes exposing phosphatidylserine are recognized, bound, engulfed, and degraded by macrophages. Eryptosis thus fosters clearance of affected erythrocytes from circulating blood. Iron deficiency leads to anemia, in part by decreasing erythrocyte life span. In this study, phosphatidylserine exposure, cell size, and cytosolic Ca 2+ were measured by FACS analysis of annexin‐V binding, forward scatter, and Fluo‐3 fluorescence, respectively. Erythrocytes from mice on control diet were compared with erythrocytes from mice exposed 10 weeks to iron‐deficient diet. Iron deficiency significantly ( P <0.001) enhanced erythrocyte annexin‐V binding (from 2.4 to 3.7%), decreased forward scatter (from 544 to 393), and increased cytosolic Ca 2+ concentration. 45 Ca 2+ flux measurements and patch clamp experiments revealed enhanced Ca 2+ uptake (by 2.3‐fold) and cation channel activity. The half‐life of fluorescence‐labeled, iron‐deficient, or Ca 2+ ‐loaded erythrocytes was significantly reduced compared with control erythrocytes. Thus, the experiments reveal a novel mechanism triggered by iron deficiency, which presumably contributes to accelerated clearance of erythrocytes in iron deficiency anemia.