HEART-CELLS IN CULTURE - A MODEL OF MYOCARDIAL IRON OVERLOAD AND CHELATION

Abstract

The effect of Fe loading and chelation was studied in heart cell cultures obtained from newborn rats. Radioactive Fe uptake/2 .times. 106 cells/24 h was 3.8% for 59Fe-transferrin, 15.8% for 59Fe-ferric ammonium citrate (FeAC) at 20 .mu.g Fe/ml in 20% serum, and 37.1% for 59FeAC at 20 .mu.g Fe/ml in serum-free medium. About 1/3 of the cellular radioactive Fe was in ferritin and the rest in an insoluble lysosomal fraction. Fe uptake was almost completely inhibited by reducing the incubation temperature from 37.degree. C to 10.degree. C. Intracellular concentrations of malondialdehyde (MDA) were doubled after 15 min of Fe loading and reached maximal concentrations at 3 h. Fe mobilization by deferoxamine at concentrations ranging from 0.025 mmol/l to 0.3 mmol/l resulted in normalization of cellular MDA concentrations, in direct proportion to the amounts of Fe removed. Cultured myocardial cells are evidently able to assimilate large amounts of nontransferrin Fe and that Fe uptake and mobilization are associated with striking changes in lipid peroxidation as manifested by the respective increase and decrease in cellular MDA concentrations.