Zhan H, Pollack S, Weaver J
Dept. of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.
Eur J Haematol. 1990 Jul;45(1):15-8. doi: 10.1111/j.1600-0609.1990.tb00408.x.
We have demonstrated that the intracellular processing of transferrin to effect iron removal involves two pathways, one sensitive to rotenone and the other not. We have also found that the effect of the rotenone is dependent on the transferrin concentration: iron uptake was suppressed with concentrations of transferrin in the micromolar range, and was not suppressed at physiologic concentrations of transferrin. Rotenone does not disturb transferrin's interaction with its extracellular receptor, indicating that its action must be intracellular. The following model is suggested: that separate pathways are entered by transferrin in the cell. The first pathway is preferentially utilized when transferrin is in short supply. It begins with an intracellular site which has a high affinity (and low capacity) for either iron or transferrin. The second pathway begins with an intracellular site which has a high capacity (but low affinity) for either iron or transferrin and is utilized when transferrin is in physiologic concentration (and the low-capacity, high-affinity site is saturated); the pathway it initiates is dominant when transferrin is abundant. We speculate that the high-affinity low-capacity pathway may serve to direct intracellular iron to sites which would be critically injured by iron excess.
我们已经证明，转铁蛋白的细胞内加工过程以实现铁的清除涉及两条途径，一条对鱼藤酮敏感，另一条则不敏感。我们还发现鱼藤酮的作用取决于转铁蛋白的浓度：在微摩尔范围内的转铁蛋白浓度下，铁摄取受到抑制，而在转铁蛋白的生理浓度下则未受到抑制。鱼藤酮不会干扰转铁蛋白与其细胞外受体的相互作用，这表明其作用必定发生在细胞内。提出了以下模型：转铁蛋白在细胞内进入不同的途径。当转铁蛋白供应不足时，优先利用第一条途径。它始于对铁或转铁蛋白具有高亲和力（但低容量）的细胞内位点。第二条途径始于对铁或转铁蛋白具有高容量（但低亲和力）的细胞内位点，并且在转铁蛋白处于生理浓度（并且低容量、高亲和力位点饱和）时被利用；当转铁蛋白丰富时，它启动的途径占主导地位。我们推测，高亲和力低容量途径可能用于将细胞内铁导向那些会因铁过量而受到严重损伤的位点。
