Differential accumulation of non-transferrin-bound iron by cardiac myocytes and fibroblasts

Abstract

Cardiac myocytes accumulate iron preferentially over fibroblast-like non-myocytes, both in clinical iron overload and when the cells are grown together in culture. In order to determine whether this reflects the tissue context or is an inherent property of the cells, we studied iron transporters, transport kinetics, and iron efflux in homogeneous cultures of rat cardiac myocytes and fibroblasts. In both cells, the rate of uptake of 59Fe from transferrin was insignificant, compared to the rate of uptake from non-transferrin-bound iron (NTBI). Expression of transferrin receptor mRNA and protein, and divalent metal transporter 1 (DMT1) mRNA, could not account for any difference in iron accumulation, and proportional efflux after iron loading was similar in both cells. Nevertheless, iron accumulation from NTBI over 72 h was greater in myocytes as determined by histological staining and quantitative iron measurement. NTBI uptake was greater for Fe 2+ than Fe 3+ in both cells, was increased by iron loading in both cells to a similar extent, and was characterized bysimilar Michaelis constants ( K m) in all cases (redox state and presence or absence of iron loading). However, V max values were about 10-fold higher in myocytes. We conclude that preferential iron accumulation in cardiac myocytes, compared to fibroblasts, is due to a higher capacity of the NTBI-transporter system, and reflects an inherent difference in NTBI acquisition by the individual cell types.