Erythrocyte signal transduction pathways, their oxygenation dependence and functional significance

Abstract

Erythrocytes play a key role in human and vertebrate metabolism. Tissue O 2 supply is regulated by both hemoglobin (Hb)-O 2 affinity and erythrocyte rheology, a key determinant of tissue perfusion. Oxygenationdeoxygenation transitions of Hb may lead to reorganization of the cytoskeleton and signalling pathways activation/deactivation in an O 2 -dependent manner. Deoxygenated Hb binds to the cytoplasmic domain of the anion exchanger band 3, which is anchored to the cytoskeleton, and is considered a major mechanism underlying the oxygenationdependence of several erythrocyte functions. This work discusses the multiple modes of Hb-cytoskeleton interactions. In addition, it reviews the effects of Mg 2+ , 2,3-diphosphoglycerate, NO, shear stress and Ca 2+ , all factors accompanying the oxygenationdeoxygenation cycle in circulating red cells. Due to the extensive literature on the subject, the data discussed here, pertain mainly to human erythrocytes whose O 2 affinity is modulated by 2,3-diphosphoglycerate, ectothermic vertebrate erythrocytes that use ATP, and to bird erythrocytes that use inositol pentaphosphate. Copyright © 2005 S. Karger AG, Basel.