转铁蛋白受体mRNA在MEL细胞中表达的调节  

Regulation of Transferrin Receptor mRNA Expression in MEL Cells

作　　者：王伟良[1] 李蓉生[1] 李琦[1] 

机构地区：[1]中国医学科学院,中国协和医科大学北京协和医院血液科,北京100730

出　　处：《中国实验血液学杂志》1996年第4期377-382,共6页Journal of Experimental Hematology

摘　　要：转铁蛋白受体(TfR)的主要功能是调节细胞的铁摄取量。它的表达除受细胞内铁含量影响外,在红系细胞还与血红素的合成和细胞的增殖状态有关,但在非红系细胞,则仅与细胞的增殖状态相关。本实验通过对小鼠红白血病(MEL)细胞在二甲基亚砜(DMSO)诱导分化前后、不同的铁状态和不同的血红素合成条件下,采用Northern印迹方法,观察TfR mRNA含量的变化。结果为:①在未诱导的MEL细胞,随着细胞的增殖,TfR mRNA含量增加;诱导的MEL细胞,虽然随着细胞分化成熟而丧失增殖能力,但当存在血红素合成时,TfR mRNA含量也增高,且增高幅度较非诱导组高。②在未诱导的MEL细胞,降低细胞内铁含量(培养液中加入去铁胺式抗TfR单克隆抗体),可刺激TfR mRNA表达;增加细胞内铁含量(培养液中加入转铁蛋白),则抑制TfR mRNA的表达;在诱导的MEL细胞,采用相同条件的铁状态时,细胞内TfR mRNA水平发生类似的改变,但变化的程度较小。③在未诱导的MEL细胞,加入血红素合成抑制剂(培养液中加入异烟肼),不改变TfR mRNA的表达;在诱导的MEL细胞,血红素合成抑制剂既抑制红系细胞的分化,也抑制TfR mRNA的表达。④当培养液中加入EPO,则促进诱导的MEL细胞内TfR mRNA的表达。上述结果提示,在红系细胞,TfR mRNA的表达除受细胞内铁调节外。Transferrin receptor which is a membrane receptor plays a key role in the control of iron uptake following requirement for specific cellular functions. TfR numbers are positively correlated with proli-feration in non - erythroid, while TfR numbers in hemoglobin - synthesizing celis increase during diferentiation and are, therefore, negatively correlated with proliferation. In the present study, we studied changes of TfR mRNA Ievels, with Northern blot, under the condition of different iron sta-tuses and heme - synthesizing in non - induced and induced MEL celis with DMSO. The results were: ① When celis proliferate, TfR mRNA levels increased in non - induced MEL celis. In induced MEL cells, althrough celis stop proliferating, because of heme - synthesizing, TfR mRNA Ievels increased, too. ② The amount of intracellular iron regulates TfR mRNA expression in non ' induced and induced MEL cells: when iron was in excess, (added transferrin to cultural medium), the TfR mRNA levels decreased; when iron was in deficiency (added deferrioxamine or anti - TfR McAb to cultural medium), the TfR mRNA Ievels increased. Changeable degree of TfR mRNA Ievels regulated by intracellular iron in non - induced celis is higher than one in induced cells. ③The inhibition of heme synthesis in induced cells at the level of 5 - aminolevulinic acid synthase by INH decreased the expression of TfR mRNA. ④ The stimulation of erythropoiesis is by EPO increased the expression of TfR mRNA in induced MEL cells. Thus, these studies indicated that the expression of TfR mRNA in erythroid cells were regulated by both the Ievel of intracellular iron and the synthesis of heme.

关 键 词：转铁蛋白受体 MRNA 红系细胞 小鼠红白血病 血红素合成 

分 类 号：R329[医药卫生—人体解剖和组织胚胎学]