Rybner C, Hillion J, Sahraoui T, Lanotte M, Botti J
INSERM U-496, Institut Universitaire d'Hématologie (IUH), Hôpital Saint-Louis, Paris, France.
Leukemia. 2002 May;16(5):940-8. doi: 10.1038/sj.leu.2402443.
The cellular prion protein (PrPc) is a sialoglycoprotein involved in the pathogenesis of prion diseases. It has been identified at the plasma membrane of several cell types. All-trans retinoic acid (ATRA) is known to induce differentiation of human leukemia cell lines in vitro. PrPc messenger ribonucleic acid (mRNA) and protein are down-regulated upon ATRA-induced differentiation of HL60 cells. In this report, we have investigated the regulation of PrPc mRNA and protein expression during ATRA-treatment of maturation-sensitive (NB4) and -resistant (NB4-R1 and NB4-R2) cell lines. In ATRA-induced maturation of NB4 cells, down-regulation of PrPc mRNA and protein were observed. We also show that down-regulation of PrPc mRNA is dependent on protein synthesis. Moreover, the same down-regulation of prion protein by ATRA was observed at the surface of maturation-resistant, ATRA-responsive NB4-R1 cells. In contrast, the maturation-resistant and ATRA-unresponsive NB4-R2 subline showed no variation in membrane prion protein expression. These results demonstrate a dissociation between the regulation of prion protein expression by ATRA and the process of granulocyte maturation. We propose that retinoids should be investigated further as a preventive strategy to slow down prion disease progression.
细胞朊蛋白（PrPc）是一种参与朊病毒疾病发病机制的唾液酸糖蛋白。它已在多种细胞类型的质膜上被鉴定出来。全反式维甲酸（ATRA）已知在体外可诱导人白血病细胞系分化。在HL60细胞经ATRA诱导分化后，PrPc信使核糖核酸（mRNA）和蛋白表达下调。在本报告中，我们研究了在对成熟敏感的（NB4）和耐药的（NB4-R1和NB4-R2）细胞系进行ATRA处理期间PrPc mRNA和蛋白表达的调控情况。在ATRA诱导NB4细胞成熟过程中，观察到PrPc mRNA和蛋白表达下调。我们还表明，PrPc mRNA的下调依赖于蛋白质合成。此外，在耐药且对ATRA有反应的NB4-R1细胞表面也观察到了ATRA对朊蛋白的相同下调作用。相比之下，耐药且对ATRA无反应的NB4-R2亚系的膜朊蛋白表达没有变化。这些结果表明ATRA对朊蛋白表达的调控与粒细胞成熟过程之间存在脱节。我们建议应进一步研究视黄酸作为减缓朊病毒疾病进展的预防策略。
