Di Pietro Roberta, di Giacomo Viviana, Caravatta Luciana, Sancilio Silvia, Rana Rosa Alba, Cataldi Amelia
Dipartimento di Biomorfologia, Chieti-Pescara, Italy.
J Cell Biochem. 2007 Mar 1;100(4):1070-9. doi: 10.1002/jcb.21106.
K562 are human erythroleukemia cells inducible to differentiate into megakaryocytic or erythroid lineage by different agents. Cyclic nucleotide Response Element Binding (CREB) protein, a nuclear transcription factor which mediates c-AMP signaling, is a potential candidate involved in the occurrence of erythroid differentiation and adaptive response. Here we investigated signaling events in K562 cells induced with 30 microM hemin to undergo erythroid differentiation. CREB activation was detected early 1 h after hemin treatment and up to 4 and 6 days of treatment, when K562 terminal differentiation occurs together with caspase-3 maximal activation and PARP degradation. It was interesting to note that after hemin treatment in the presence of SB203580, p38 MAP kinase specific inhibitor, a reduced rate of CREB phosphorylation as well as a lower percentage of CD71/Gly+ (Glycophorin A) cells were detectable, demonstrating the p38 MAP kinase dependency of these phenomena. All in all these results document a novel relationship between CREB activation and differentiation-related apoptotic cell death and assign a role to p38 MAP kinase pathway in determining these events in K562 erythroleukemia cells.
K562是一种人类红白血病细胞，可通过不同试剂诱导分化为巨核细胞或红细胞系。环磷酸核苷酸反应元件结合（CREB）蛋白是一种介导c-AMP信号传导的核转录因子，是参与红细胞分化和适应性反应发生的潜在候选因子。在此，我们研究了用30微摩尔血红素诱导K562细胞进行红细胞分化过程中的信号事件。在血红素处理后1小时早期即可检测到CREB激活，且在处理4天和6天时仍可检测到，此时K562细胞发生终末分化，同时caspase-3最大程度激活和PARP降解。值得注意的是，在存在p38 MAP激酶特异性抑制剂SB203580的情况下进行血红素处理后，可检测到CREB磷酸化速率降低以及CD71/糖蛋白A（血型糖蛋白A）细胞百分比降低，这表明这些现象依赖于p38 MAP激酶。总而言之，这些结果证明了CREB激活与分化相关的凋亡性细胞死亡之间存在新的关系，并确定了p38 MAP激酶途径在K562红白血病细胞中决定这些事件的作用。
