ABSTRACT
The level of inositol 1,4,5-trisphosphate (Ins1,4,5P3) was determined in human and rabbit red blood cells of different ages. In human erythrocytes, fractionated by discontinuous density gradient centrifugation, Ins1,4,5P3 was 290 nM in the 0.3% low density (youngest) cells compared to values of 107 nM in the whole red blood cell population. A progressive increase in Ins1,4,5P3 was then observed during erythrocyte aging from values of 63 nM in mature erythrocytes to 128 nM in the oldest cells. Determinations of Ins1,4,5P3 in rabbit erythrocytes provided values of 180 nM. Phenylhydrazine was administered to three animals to induce reticulocytosis. Ins1,4,5P3 in rabbit reticulocytes was significantly lower than in the whole red cell population, remained lower in young red blood cells and then increased to normal values during cell maturation. These results provide evidence for an increase of Ins1,4,5P3 during red blood cell aging and could contribute to explain the age-dependent loss of deformability and of Ca2+ homeostasis of these cells.
Subject(s)
Erythrocyte Aging/physiology , Erythrocytes/metabolism , Inositol 1,4,5-Trisphosphate/blood , Animals , Calcium/blood , Erythrocyte Deformability/physiology , Glucosephosphate Dehydrogenase/blood , Humans , Rabbits , Reticulocytes/metabolism , Species SpecificityABSTRACT
Hereditary spherocytosis (HS) is characterised with many deviations of red blood cells properties. We investigated a group of 14 patients with mild HS, 7 of whom were splenectomised. We found changes in the content and/or turnover of polyphosphoinositides and phosphatidic acid accompanied by the higher generation of inositol 1,4,5-trisphosphate. We suggest that the activation of the phosphoinositide signalling system may be crucial for the manifestation of HS.
Subject(s)
Erythrocytes/metabolism , Phosphatidylinositol Phosphates , Phosphatidylinositols/blood , Signal Transduction , Spherocytosis, Hereditary/blood , Calcium/blood , Humans , Inositol 1,4,5-Trisphosphate/blood , Phosphates/blood , Phosphatidic Acids/blood , Phosphatidylinositols/physiology , Second Messenger Systems/physiology , SplenectomyABSTRACT
Human erythrocytes contain 217.2 +/- 70.5 pmole of inositol 1,4,5-trisphosphate per ml of packed cells (n = 14). The increased generation of Ins 1,4,5P3, was induced by 1 microM A 23187, 20 microM Pb2+, and by AlF4-. Ins 1,4,5P3, Pb2+ and AlF4- evoke shape changes, disorganisation of spectrin network and vesiculation. In erythrocytes of patients with hereditary spherocytosis the level of Ins 1,4,5P3 was increased to 556.7 +/- 374 pmole per ml of packed cells. We suggest that activation of the phosphoinositide signalling system may represent a common denominator for many divergent stimuli and defects which affect shape changes of erythrocytes.
