Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expression.
Transferrin receptor-independent uptake of differic transferrin by human hepatoma cells with antisense inhibition of receptor expression.
复制标题
人肝癌细胞不依赖转铁蛋白受体摄取不同的转铁蛋白，并反义抑制受体表达。
DOI：
10.1053/jhep.1996.v23.pm0008675172
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Aisen,P
中科院分区：
文献类型：
--
作者：
Trinder,D;Zak,O;Aisen,P
The hepatic uptake of transferrin‐bound iron by a nontransferrin receptor (NTR)‐mediated process was investigated using the human hepatoma cell line HuH7. Because HuH7 cells also acquire iron from transferrin by a receptor (TR)‐mediated process, TR expression was inhibited by transfecting the cells with a plasmid containing human TR complementary DNA in antisense orientation relative to a human cytomegalovirus promoter/enhancer element. Cell clones were obtained that expressed a 50% to 60% reduction in cell surface TR, leading to a corresponding decrease in transferrin and iron uptake compared with wild‐type cells. Uptake of transferrin by a second process was nonsaturable and not inhibited by a 100‐fold excess of unlabeled transferrin. The amounts of transferrin taken up by the wild‐type and antisense cells by this process were similar, showing that it did not involve TR. The proteolytic enzyme Pronase reduced the uptake of transferrin, suggesting that the NTR‐mediated process entailed the nonsaturable binding of transferrin to plasma membrane proteins. This process, like the TR‐mediated one, involved the internalization and recycling of transferrin, leading to accumulation of iron with time. Iron uptake mediated by NTR process was saturable and displaced by 100‐fold excess unlabeled transferrin and reduced by weak bases and metabolic inhibitors. Therefore, the NTR‐mediated process entailed transferrin adsorption to membrane‐bound proteins, internalization, and release of iron from transferrin by a pH‐dependent step followed by the intracellular transport of iron into ferritin and heme by a saturable carrier‐mediated mechanism.
