Amyloid-beta peptide affects the oxygen dependence of erythrocyte metabolism: A role for caspase 3

Human erythrocyte metabolism is modulated by the cell oxygenation state. Among other mechanisms, competition of deoxyhemoglobin and some glycolytic enzymes for the cytoplasmic domain of band 3 is probably involved in modulation. This metabolic modulation is connected to variations in intracellular NADPH and ATP levels as a function of the oxygenation state of the cell, and, consequently, it should have physiologic relevance. The present study investigates the effect of amyloid-beta peptide exposure on this metabolic modulation and its relationship with the activity of erythrocyte caspase 3. Metabolic differences between erythrocytes incubated at high and low oxygen saturation disappear following to 24h exposure to amyloid-beta peptide. Western blotting analysis shows that caspase 3 is concurrently activated. Pre-incubation of amyloid-beta peptide-treated erythrocytes with a specific inhibitor of caspase 3, partially restores the oxygen-dependent modulation. This finding suggests that human erythrocytes following to exposure to amyloid-beta peptide show a complete loss of the oxygen-dependent metabolic modulation, which is partially restored by caspase 3 inhibitor-treatment.