Crosby J S, Lee K, London I M, Chen J J
Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
Mol Cell Biol. 1994 Jun;14(6):3906-14. doi: 10.1128/mcb.14.6.3906-3914.1994.
The role of heme-regulated eIF-2 alpha kinase (HRI) in the regulation of protein synthesis in rabbit reticulocytes is well documented. Inhibitors of protein synthesis with properties similar to those of HRI have been described in some nonerythroid cell types, but it has not yet been determined whether these eIF-2 alpha kinase activities are mediated by HRI or one or more as yet uncharacterized kinases. We have studied the expression of mRNA, polypeptide, and kinase activities of HRI in various tissues from both nonanemic and anemic rabbits. Our results indicate that HRI is expressed in an erythroid cell-specific manner. HRI is present in the bone marrow and peripheral blood of both nonanemic and anemic rabbits but not in any of the other tissues tested. HRI mRNA is present at low levels in uninduced mouse erythroleukemic (MEL) cells and human K562 cells and accumulates to higher levels upon induction. The accumulation of HRI mRNA in differentiating MEL cells is dependent upon the presence of heme. The addition of 3-amino-1,2,4-triazole (AT), an inhibitor of heme biosynthesis, to the induction medium markedly reduced HRI mRNA accumulation. Simultaneous addition of hemin and AT to the dimethyl sulfoxide induction medium largely prevented the inhibition of HRI mRNA induction by AT. These findings indicate that HRI is expressed in an erythroid cell-specific manner and that the major physiologic role of HRI is in adjusting the synthesis of globins to the availability of heme.
血红素调节的真核起始因子2α激酶（HRI）在兔网织红细胞蛋白质合成调控中的作用已有充分记载。在一些非红细胞类型中已描述了具有与HRI相似特性的蛋白质合成抑制剂，但尚未确定这些真核起始因子2α激酶活性是由HRI介导，还是由一种或多种尚未鉴定的激酶介导。我们研究了非贫血和贫血兔各种组织中HRI的mRNA、多肽表达及激酶活性。我们的结果表明，HRI以红细胞特异性方式表达。HRI存在于非贫血和贫血兔的骨髓和外周血中，但在所检测的其他任何组织中均不存在。HRI mRNA在未诱导的小鼠红白血病（MEL）细胞和人K562细胞中含量较低，诱导后积累至较高水平。分化的MEL细胞中HRI mRNA的积累依赖于血红素的存在。向诱导培养基中添加血红素生物合成抑制剂3-氨基-1,2,4-三唑（AT）可显著降低HRI mRNA的积累。同时向二甲基亚砜诱导培养基中添加血红素和AT可在很大程度上防止AT对HRI mRNA诱导的抑制作用。这些发现表明，HRI以红细胞特异性方式表达，且HRI的主要生理作用是根据血红素的可利用性调节珠蛋白的合成。
