Trinder D, Morgan E
Department of Physiology, University of Western Australia, Nedlands.
Hepatology. 1997 Sep;26(3):691-8. doi: 10.1053/jhep.1997.v26.pm0009303500.
The liver acquires iron from transferrin by transferrin receptor-mediated (TR) and transferrin receptor-independent pathways (NTR) and from nontransferrin-bound iron (NTB-Fe). Iron uptake by the NTR processes involves an iron-carrier mediated step. Experiments, using human hepatoma cells (HuH7) transfected with TR antisense (sense for control) RNA expression vectors to suppress TR expression, were performed to examine the effect of unlabeled NTB-Fe as iron citrate on the uptake of 59Fe-125I-transferrin. This was to determine if the uptake of transferrin-bound iron (Tf-Fe) and NTB-Fe uptake is mediated by a common iron-carrier. Iron citrate inhibited the uptake of 59Fe-transferrin (2.5 micromol/L Fe) in a concentration-dependent manner with a maximum effect when the citrate-iron:Tf-Fe molar ratio was 10:1. Transferrin uptake was not affected. At a lower Tf-Fe concentration of (0.125 micromol/L) when uptake of iron is TR-mediated, a 10-fold molar excess of iron citrate had no effect on Tf-Fe uptake by HuH7 TR antisense and sense cells. However, at a higher Tf-Fe concentration (2.5 micromol/L), when uptake occurs mainly by the NTR-mediated process, there was a 40% reduction in the membrane-bound and intracellular uptake of iron. Iron citrate did not affect the maximum rate (Vmax) of Tf-Fe uptake but the Michaelis-Menten constant (Km) for Tf-Fe uptake by the NTR-mediated process was increased, indicating there was competitive inhibition of Tf-Fe uptake by iron citrate. These results suggest that the uptake of NTB-Fe and Tf-Fe by the NTR- mediated process occurs by the same cellular pathway, using a common iron-carrier.
肝脏通过转铁蛋白受体介导的（TR）和不依赖转铁蛋白受体的途径（NTR）从转铁蛋白获取铁，并从不与转铁蛋白结合的铁（NTB-Fe）中获取铁。NTR过程的铁摄取涉及铁载体介导的步骤。进行了实验，使用转染了TR反义（对照为正义）RNA表达载体以抑制TR表达的人肝癌细胞（HuH7），来检测未标记的作为柠檬酸铁的NTB-Fe对59Fe-125I-转铁蛋白摄取的影响。这是为了确定转铁蛋白结合铁（Tf-Fe）的摄取和NTB-Fe的摄取是否由共同的铁载体介导。柠檬酸铁以浓度依赖的方式抑制59Fe-转铁蛋白（2.5微摩尔/升铁）的摄取，当柠檬酸铁与Tf-Fe的摩尔比为10:1时具有最大效应。转铁蛋白的摄取不受影响。在较低的Tf-Fe浓度（0.125微摩尔/升）下，当铁的摄取由TR介导时，10倍摩尔过量的柠檬酸铁对HuH7 TR反义细胞和正义细胞摄取Tf-Fe没有影响。然而，在较高的Tf-Fe浓度（2.5微摩尔/升）下，当摄取主要通过NTR介导的过程发生时，膜结合和细胞内铁摄取减少了40%。柠檬酸铁不影响Tf-Fe摄取的最大速率（Vmax），但NTR介导过程中Tf-Fe摄取的米氏常数（Km）增加，表明柠檬酸铁对Tf-Fe摄取存在竞争性抑制。这些结果表明，NTR介导的过程对NTB-Fe和Tf-Fe的摄取通过相同的细胞途径发生，使用共同的铁载体。
