Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line
Autophagy is an important event for megakaryocytic differentiation of the chronic myelogenous leukemia K562 cell line
复制标题
DOI：
10.4161/auto.5.8.9889
复制
发表时间：
2009-11-16
期刊：
影响因子：
13.3
通讯作者：
Auberger, Patrick
中科院分区：
文献类型：
--
作者：
Colosetti, Pascal;Puissant, Alexandre;Auberger, Patrick
自噬是一种高度保守的分解代谢过程，以细胞器和大分子的消除和循环为特征，其特征是形成称为自噬小体的双膜小泡。迄今为止，自噬在细胞分化中的作用鲜有文献记载。在这里，我们研究了慢性粒细胞白血病(CML)细胞系K562的巨核细胞分化的可能性，这一已知伴随着细胞内空泡积累的过程可能涉及自噬。使用不同的互补方法，我们发现佛波酯PMA和p38(MAPK)抑制剂SB202190(SB)的结合，使大多数K562细胞走向巨核血统，也触发了空泡化和自噬。PMA+Sb的组合似乎既引起自噬通量的增加，又引起自噬降解的阻断。自噬的诱导还伴随着Beclin 1和p62/SQSTMI表达的增加，并被发现在巨核细胞分化开始之前。此外，Lc3和Beclin 1被特定的siRNA敲除后，PMA+Sb介导的空泡化、Lc3-II积聚和巨核细胞分化也受到抑制。据我们所知，这是第一次描述诱导自噬参与K562的巨核细胞分化。慢性粒细胞白血病细胞。
Autophagy is a highly conserved catabolic process for the elimination and recycling of organelles and macromolecules, characterized by the formation of double-membrane vesicles called autophagosomes. To date, the function of autophagy in cell differentiation is poorly documented. Here, we investigated the possibility that megakaryocytic differentiation of the Chronic Myelogenous Leukemia (CML) cell line K562, a process known to be accompanied by accumulation of vacuoles inside the cells, might involve autophagy. Using various complementary approaches, we show that the combination of the phorbol ester PMA and the p38(MAPK) inhibitor SB202190 (SB), which engaged a majority of K562 cells towards the megakaryocytic lineage, also triggered vacuolization and autophagy. The combination of PMA + SB appears to induce both increase in autophagic fluxes and an autophagic degradation blockage. Induction of autophagy was accompanied also by increased expression of Beclin 1 and p62/SQSTMI and was found to precede the onset of megakaryocytic differentiation. Moreover, knockdown of LC3 and Beclin 1 by specific siRNAs impaired PMA + SB-mediated vacuolization, LC3-II accumulation and megakaryocytic differentiation, as well. To the best of our knowledge, this is the first description that induction of autophagy is involved in megakaryocytic differentiation of K562. CML cells.