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[大鼠铁状态对肝细胞中铁蛋白和转铁蛋白合成的调节]

[Regulation of ferritin and transferrin synthesis in hepatocytes depending on iron status of rats].

作者信息

Nakagawa Y

出版信息

Nihon Ika Daigaku Zasshi. 1989 Oct;56(5):494-503. doi: 10.1272/jnms1923.56.494.

Abstract

In order to examine the control mechanism of ferritin (Fr) and transferrin (Tf) synthesis depending on intracellular iron levels, the rate of 14C-leucine incorporation into those proteins was investigated by cell culture of isolated hepatocytes obtained from iron deficient, iron injected and control rats. The effects of iron (ferric ammonium citrate: FeAc) and (diferric Tf: 2FeTf) or desferrioxamine (Dfo) in culture media were also examined. Serum iron, TIBC and Hb levels of iron deficient rats, which were fed an iron deficient diet for 2 and 4 weeks were significantly lower than the control. However serum iron and TIBC levels of iron injected rats which had received 30 and 45 mg iron as iron dextran 18 h before sacrifice were approximately ten times higher than the control group. The time course of 14C-leucine incorporation into Fr and Tf was investigated at the 60, 120 and 180 minutes stages of the culture. Fr synthesis was increased by the amounts of iron injected, whereas Tf synthesis showed a negative response to iron. The 14C activities in Fr and Tf detected from culture media were proportional to those in hepatocytes. The percentage of nonglycosylated Fr was 82.0-91.4% for total Fr in the culture media in every experiment, which was measured by the affinity of glycosylated Fr to Con A-Sepharose (Con A). This result suggested the leakage of cytosol Fr through the cell membrane instead of specific secretion of the sialyl protein. The efficiency of Fr and Tf synthesis was positively or negatively proportional to cellular iron contents respectively. And the curves of 14C-leucine incorporation into both proteins, calculated as the sum of those in hepatocytes and culture media intersected at the point between the 30 mg iron injected and control groups. The addition of FeAC or 2FeTf into the culture media had an indistinct effect on Fr and Tf synthesis, whereas there was a significant decrease for Fr and a slight increase for Tf formations in the Dfo supplement. These results showed the influence of cellular iron levels in Fr and Tf synthesis.

摘要

为了研究铁蛋白(Fr)和转铁蛋白(Tf)合成的调控机制如何依赖于细胞内铁水平,通过对从缺铁、注射铁剂和对照大鼠分离得到的肝细胞进行细胞培养,研究了14C-亮氨酸掺入这些蛋白质的速率。同时也检测了培养基中铁(柠檬酸铁铵:FeAc)和(双铁转铁蛋白:2FeTf)或去铁胺(Dfo)的作用。喂养缺铁饮食2周和4周的缺铁大鼠的血清铁、总铁结合力(TIBC)和血红蛋白水平显著低于对照组。然而,在处死前18小时接受30毫克和45毫克右旋糖酐铁注射的注射铁剂大鼠的血清铁和TIBC水平比对照组高约10倍。在培养的60、120和180分钟阶段研究了14C-亮氨酸掺入Fr和Tf的时间进程。Fr的合成随着注射铁量的增加而增加,而Tf的合成对铁呈负反应。从培养基中检测到的Fr和Tf中的14C活性与肝细胞中的活性成比例。在每个实验中,培养基中总Fr的非糖基化Fr百分比为82.0 - 91.4%,这是通过糖基化Fr与刀豆球蛋白A-琼脂糖(Con A)的亲和力来测量的。该结果表明胞质Fr通过细胞膜渗漏,而非唾液酸蛋白的特异性分泌。Fr和Tf合成的效率分别与细胞内铁含量呈正相关或负相关。并且,计算为肝细胞和培养基中14C-亮氨酸掺入量之和的两种蛋白质的14C-亮氨酸掺入曲线在注射30毫克铁组和对照组之间的点相交。向培养基中添加FeAC或2FeTf对Fr和Tf合成的影响不明显,而在添加Dfo时,Fr的合成显著降低,Tf的合成略有增加。这些结果显示了细胞内铁水平对Fr和Tf合成的影响。

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