Liu Ying, Parkes Joel G, Templeton Douglas M
Department of Laboratory Medicine and Pathobiology, University of Toronto, Medical Sciences Building Rm 6302, 1 King's College Circle, M5S 1A8, Toronto, Canada.
J Mol Cell Cardiol. 2003 May;35(5):505-14. doi: 10.1016/s0022-2828(03)00072-5.
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 Fe2+ than Fe3+ 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.
在临床铁过载以及细胞在培养中共同生长时，心肌细胞比成纤维细胞样非心肌细胞更优先积累铁。为了确定这是反映了组织环境还是细胞的固有特性，我们研究了大鼠心肌细胞和成纤维细胞的同质培养物中的铁转运蛋白、转运动力学和铁外流。在两种细胞中，与从非转铁蛋白结合铁（NTBI）的摄取速率相比，从转铁蛋白摄取59Fe的速率微不足道。转铁蛋白受体mRNA和蛋白以及二价金属转运体1（DMT1）mRNA的表达无法解释铁积累的任何差异，并且两种细胞在铁加载后的比例外流相似。然而，通过组织学染色和定量铁测量确定，心肌细胞中NTBI在72小时内的铁积累更多。在两种细胞中，Fe2+的NTBI摄取量均大于Fe3+，两种细胞中的铁加载均使其摄取量增加到相似程度，并且在所有情况下（氧化还原状态以及有无铁加载）均具有相似的米氏常数（K(m)）。然而，心肌细胞中的V(max)值约高10倍。我们得出结论，与成纤维细胞相比，心肌细胞中优先积累铁是由于NTBI转运系统的能力更高，并且反映了个体细胞类型在获取NTBI方面的固有差异。
