Trentesaux C, Gérard B, Mayeux P, Jeannesson P, Jacquot R, Jardillier J C
GIBSA, Laboratoires de Biochimie, Faculté de Pharmacie et Reims, France.
Biochim Biophys Acta. 1989 Jul 11;1012(2):161-5. doi: 10.1016/0167-4889(89)90090-6.
The human leukemic cell line K 562 can be induced to differentiate along the erythroid lineage by various chemical compounds and particularly by the anthracyclic antitumor drug, adriamycin (ADR). In this study, we show that, in the presence of a subtoxic concentration of ADR (30 nM), the appearance of hemoglobin-producing K 562 cells is associated with a specific increase in globin mRNA accumulation corresponding to epsilon-, zeta-, gamma-, alpha-globin chains. At the translational level, bulk protein synthesis is strongly decreased following ADR treatment, whereas globin chain synthesis is specifically enhanced. Globin chains represent about 20% of total proteins in ADR-treated cells, versus about 3.5% in controls on day 3. Similarly, on day 3, heme synthesis (55Fe incorporation) is about 10-times higher in ADR-treated cells than in control cells (20,888 dpm/10(5) cells versus 1693 dpm/10(5) cells) which confirms the increase in heme content (420 pM/10(6) treated cells versus 100 pM/10(6) control cells). In the presence of succinylacetone, a heme synthesis inhibitor which prevented the differentiating effects of ADR, the globin mRNA accumulation was not affected. This suggests that heme did not play a regulatory role in globin mRNA transcription, a result at variance with observations published by others. Such results strongly support the notion that in addition to cytostatic properties, ADR stimulates specifically globin and heme synthesis.
人白血病细胞系K 562可被多种化合物诱导沿红系分化，尤其是蒽环类抗肿瘤药物阿霉素（ADR）。在本研究中，我们发现，在亚毒性浓度的ADR（30 nM）存在下，产生血红蛋白的K 562细胞的出现与对应于ε-、ζ-、γ-、α-珠蛋白链的珠蛋白mRNA积累的特异性增加相关。在翻译水平上，ADR处理后总蛋白合成强烈下降，而珠蛋白链合成则特异性增强。在第3天，ADR处理细胞中珠蛋白链占总蛋白的约20%，而对照细胞中约为3.5%。同样，在第3天，ADR处理细胞中的血红素合成（55Fe掺入）比对照细胞高约10倍（20,888 dpm/10(5)细胞对1693 dpm/10(5)细胞），这证实了血红素含量的增加（420 pM/10(6)处理细胞对100 pM/10(6)对照细胞）。在存在琥珀酰丙酮（一种血红素合成抑制剂，可阻止ADR的分化作用）的情况下，珠蛋白mRNA积累不受影响。这表明血红素在珠蛋白mRNA转录中不发挥调节作用，这一结果与其他人发表的观察结果不同。这些结果有力地支持了这样一种观点，即除了细胞生长抑制特性外，ADR还特异性刺激珠蛋白和血红素合成。
