Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Maintenance: Tuesday, 5.7.2016, 07:00-08:00

Maintenance work on ZORA and JDB on Tuesday, 5th July, 07h00-08h00. During this time there will be a brief unavailability for about 1 hour. Please be patient.

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-14319

Akel, A; Wagner, C A; Kovacikova, J; Kasinathan, R S; Kiedaisch, V; Koka, S; Alper, S L; Bernhardt, I; Wieder, T; Huber, S M; Lang, F (2007). Enhanced suicidal death of erythrocytes from gene-targeted mice lacking the Cl-/HCO(3)(-) exchanger AE1. American Journal of Physiology. Cell Physiology, 292(5):C1759-C1767.

View at publisher


Genetic defects of anion exchanger 1 (AE1) may lead to spherocytic erythrocyte morphology, severe hemolytic anemia, and/or cation leak. In normal erythrocytes, osmotic shock, Cl(-) removal, and energy depletion activate Ca(2+)-permeable cation channels with Ca(2+)-induced suicidal erythrocyte death, i.e., surface exposure of phosphatidylserine, cell shrinkage, and membrane blebbing, all features typical for apoptosis of nucleated cells. The present experiments explored whether AE1 deficiency favors suicidal erythrocyte death. Peripheral blood erythrocyte numbers were significantly smaller in gene-targeted mice lacking AE1 (AE1(-/-) mice) than in their wild-type littermates (AE1(+/+) mice) despite increased percentages of reticulocytes (AE1(-/-): 49%, AE1(+/+): 2%), an indicator of enhanced erythropoiesis. Annexin binding, reflecting phosphatidylserine exposure, was significantly larger in AE1(-/-)erythrocytes/reticulocytes (approximately 10%) than in AE1(+/+) erythrocytes (approximately 1%). Osmotic shock (addition of 400 mM sucrose), Cl(-) removal (replacement with gluconate), or energy depletion (removal of glucose) led to significantly stronger annexin binding in AE1(-/-) erythrocytes/reticulocytes than in AE1(+/+) erythrocytes. The increase of annexin binding following exposure to the Ca(2+) ionophore ionomycin (1 muM) was, however, similar in AE1(-/-) and in AE1(+/+) erythrocytes. Fluo3 fluorescence revealed markedly increased cytosolic Ca(2+) permeability in AE1(-/-) erythrocytes/reticulocytes. Clearance of carboxyfluorescein diacetate succinimidyl ester-labeled erythrocytes/reticulocytes from circulating blood was more rapid in AE1(-/-) mice than in AE1(+/+) mice and was accelerated by ionomycin treatment in both genotypes. In conclusion, lack of AE1 is associated with enhanced Ca(2+) entry and subsequent scrambling of cell membrane phospholipids.


12 citations in Web of Science®
14 citations in Scopus®
Google Scholar™



126 downloads since deposited on 20 Mar 2009
38 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Date:May 2007
Deposited On:20 Mar 2009 15:55
Last Modified:05 Apr 2016 13:03
Publisher:American Physiological Society
Publisher DOI:10.1152/ajpcell.00158.2006
Official URL:http://ajpcell.physiology.org/cgi/reprint/292/5/C1759
PubMed ID:17251326

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page