Sasaki D, Kosunago S, Mikami T, Matsumoto T, Suzuki M
Department of Microbiology, Tohoku College of Pharmacy, Sendai, Japan.
Biol Pharm Bull. 1994 May;17(5):586-90. doi: 10.1248/bpb.17.586.
To determine the mechanism of the growth inhibition associated with the induction of erythroid differentiation in K562 cells by hemin, we used two K562 subclones with different hemoglobin (Hb)-producing activity. Hemin strongly inhibited the growth of K562-L, which had a low Hb-producing activity, but not that of K562-H, which had a high Hb-producing activity. When the cell growth of K562-L was inhibited by hemin, the S phase of the cell cycle decreased and the G2/M phase increased. In contrast, hemin had no effect on the cell cycle of K562-H. Without hemin treatment, the alpha-globin mRNA level was related to the degree of Hb production in K562-L and -H but the gamma-globin mRNA level was not. With hemin treatment, there was no increase in the alpha-globin mRNA level in K562-L but there was an increase in K562-H. The difference in alpha-globin mRNA levels correlated with the Hb production in K562-L and -H induced by hemin. The levels of c-myc and c-myb mRNAs in K562-L decreased when cell growth was strongly inhibited by hemin. These findings indicate that the growth inhibition of K562 cells by hemin is due to a suppression of the progression from the G0/G1 phase to the S phase and a delay in the G2/M phase, caused by the inhibition of c-myc and c-myb transcription. It is also affected by the Hb production, reflected in alpha-globin transcription.
为了确定氯化血红素诱导K562细胞红系分化相关的生长抑制机制，我们使用了两个具有不同血红蛋白（Hb）生成活性的K562亚克隆。氯化血红素强烈抑制Hb生成活性低的K562-L的生长，但不抑制Hb生成活性高的K562-H的生长。当K562-L的细胞生长被氯化血红素抑制时，细胞周期的S期减少，G2/M期增加。相反，氯化血红素对K562-H的细胞周期没有影响。在未用氯化血红素处理时，α-珠蛋白mRNA水平与K562-L和-K562-H中的Hb生成程度相关，但γ-珠蛋白mRNA水平则不然。在用氯化血红素处理后，K562-L中的α-珠蛋白mRNA水平没有增加，但K562-H中有增加。α-珠蛋白mRNA水平的差异与氯化血红素诱导的K562-L和-K562-H中的Hb生成相关。当细胞生长被氯化血红素强烈抑制时，K562-L中的c-myc和c-myb mRNA水平下降。这些发现表明，氯化血红素对K562细胞的生长抑制是由于c-myc和c-myb转录的抑制导致从G0/G1期到S期的进程受到抑制以及G2/M期延迟。它还受到Hb生成的影响，反映在α-珠蛋白转录中。
