Nakajima O, Iwasaki S, Hashimoto Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Cell Mol Biol (Noisy-le-grand). 1997 Feb;43(1):115-34.
We have found that protoporphyrin IX, which had been regarded as inactive, induces erythroid differentiation. The differentiation-inducing activities of various hemin-related compounds, including hematoporphyrin IX, mesoporphyrin IX, deuteroporphyrin IX and protoporphyrin IX dimethyl ester, suggested certain structural requirements for the activity: 1) the iron moiety of hemin is not essential, and 2) the propionic acid side chains of hemin play an important role. In addition, we have examined the influence of some bioactive factors on hemin/protoporphyrin IX-induced differentiation of K562 cell line. Retinoids and tubulin-disruptors dose-dependently enhanced hemin/protoporphyrin IX-induced differentiation of K562 cells, though they did not themselves induce differentiation. Retinoid antagonists suppressed hemin-induced differentiation. The effects of hemin and/or retinoids on the mRNA expressions of oncogenes (c-myc and c-myb) and retinoic acid receptor genes (rar alpha and rar beta) of K562 cells were analyzed. We also examined the possible involvement of peripheral-type benzodiazepine receptor (PBR) in hemin/protoporphyrin IX-induced differentiation of K562 cells by the use of its ligands. Diazepam itself was revealed to possess differentiation-inducing activity on K562 cells. The PBR-specific ligands modified hemin-induced differentiation. These results suggest a requirement for retinoids (or retinoid-like cofactors) for hemin/protoporphyrin IX-induced differentiation of K562 cells and the involvement of PBR in erythroid differentiation of K562 cell line.
我们发现，曾被认为无活性的原卟啉IX可诱导红系分化。包括血卟啉IX、中卟啉IX、次卟啉IX和原卟啉IX二甲酯在内的各种血红素相关化合物的分化诱导活性表明该活性具有某些结构要求：1）血红素的铁部分并非必需；2）血红素的丙酸侧链起重要作用。此外，我们研究了一些生物活性因子对血红素/原卟啉IX诱导的K562细胞系分化的影响。类视黄醇和微管蛋白破坏剂虽然自身不诱导分化，但能剂量依赖性地增强血红素/原卟啉IX诱导的K562细胞分化。类视黄醇拮抗剂可抑制血红素诱导的分化。分析了血红素和/或类视黄醇对K562细胞癌基因（c-myc和c-myb）和视黄酸受体基因（rarα和rarβ）mRNA表达的影响。我们还通过使用外周型苯二氮䓬受体（PBR）的配体，研究了PBR在血红素/原卟啉IX诱导的K562细胞分化中可能的作用。已发现地西泮本身对K562细胞具有分化诱导活性。PBR特异性配体可改变血红素诱导的分化。这些结果表明，血红素/原卟啉IX诱导K562细胞分化需要类视黄醇（或类视黄醇样辅因子），且PBR参与了K562细胞系的红系分化。
