Ho V T, Bunn H F
Division of Hematology/Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Biochem Biophys Res Commun. 1996 Jun 5;223(1):175-80. doi: 10.1006/bbrc.1996.0865.
Both in vivo and in Hep3B cells, expression of the erythropoietin gene is induced by hypoxia as well as by certain transition metals (cobalt and nickel) and by iron chelation. When Hep3B cells were incubated in an iron deficient medium, Epo mRNA expression was enhanced 4-fold compared to Hep3B cells in iron enriched medium. The increased Epo expression in iron deficient medium was abolished when Fe2-transferrin complex was added. Epo induction by cobalt was also affected by iron concentration. In iron enriched medium, erythropoietin expression in Hep3B cells was maximally induced at CoCl2 concentrations between 100 to 200 microM. In contrast, in iron poor medium, a high level of induction was obtained at a CoCl2 concentration of only 50 microM, indicating competition between iron and cobalt. Under hyperbaric oxygen, cobalt induction of erythropoietin mRNA was modestly suppressed while nickel induction was markedly enhanced. These observations support the proposal that the oxygen sensor is a heme protein in which cobalt and nickel can substitute for iron in the porphyrin ring.
在体内和Hep3B细胞中，促红细胞生成素基因的表达可由缺氧诱导，也可由某些过渡金属（钴和镍）以及铁螯合作用诱导。当Hep3B细胞在缺铁培养基中培养时，与在富铁培养基中的Hep3B细胞相比，促红细胞生成素mRNA表达增强了4倍。当添加Fe2-转铁蛋白复合物时，缺铁培养基中促红细胞生成素表达的增加被消除。钴对促红细胞生成素的诱导也受铁浓度的影响。在富铁培养基中，Hep3B细胞中促红细胞生成素的表达在100至200微摩尔的氯化钴浓度下被最大程度地诱导。相反，在缺铁培养基中，仅在50微摩尔的氯化钴浓度下就获得了高水平的诱导，表明铁和钴之间存在竞争。在高压氧下，钴对促红细胞生成素mRNA的诱导作用受到适度抑制，而镍的诱导作用则明显增强。这些观察结果支持了这样的观点，即氧传感器是一种血红素蛋白，其中钴和镍可以在卟啉环中替代铁。
