p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation
p22phox-dependent NADPH oxidase activity is required for megakaryocytic differentiation
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DOI：
10.1038/cdd.2010.67
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发表时间：
2010-12-01
影响因子：
12.4
通讯作者：
Hernandez-Hernandez, A.
中科院分区：
文献类型：
--
作者：
Sardina, J. L.;Lopez-Ruano, G.;Hernandez-Hernandez, A.
瞬时活性氧（ROS）的产生目前被证明是一个重要的机制，在细胞内信号的调节，但报告显示，在重要的生物过程，如细胞分化的ROS参与，是罕见的。在这项研究中，我们第一次表明，ROS的产生是需要在K562和HEL细胞系的巨核细胞分化，也在人CD 34（+）细胞。ROS的产生在巨核细胞分化过程中被瞬时激活，并且通过添加不同的抗氧化剂（如N-乙酰半胱氨酸、trolox、槲皮素）或烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶抑制剂二亚苯基碘鎓来消除这种产生。ROS形成的抑制阻碍了分化。RNA干扰实验表明，p22（phox）依赖性NADPH氧化酶活性是ROS产生的原因。此外，ERK、AKT和JAK 2的激活是分化所必需的，但磷脂酰肌醇3-激酶和c-Jun N-末端激酶的激活似乎不太重要。当ROS的产生被阻止时，这些信号通路的激活被部分抑制。综上所述，这些结果表明，NADPH氧化酶ROS的产生是必不可少的，参与巨核细胞发生的主要信号通路的完全激活。我们认为，这可能也是体内巨核细胞生成的重要。Cell Death and Differentiation（2010）17，1842-1854; doi：10.1038/cdd.2010.67; 2010年6月4日在线发表
Transient reactive oxygen species (ROS) production is currently proving to be an important mechanism in the regulation of intracellular signalling, but reports showing the involvement of ROS in important biological processes, such as cell differentiation, are scarce. In this study, we show for the first time that ROS production is required for megakaryocytic differentiation in K562 and HEL cell lines and also in human CD34(+) cells. ROS production is transiently activated during megakaryocytic differentiation, and such production is abolished by the addition of different antioxidants (such as N-acetyl cysteine, trolox, quercetin) or the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium. The inhibition of ROS formation hinders differentiation. RNA interference experiments have shown that a p22(phox) dependent NADPH oxidase activity is responsible for ROS production. In addition, the activation of ERK, AKT and JAK2 is required for differentiation, but the activation of phosphatidylinositol 3-kinase and c-Jun N-terminal kinase seems to be less important. When ROS production is prevented, the activation of these signalling pathways is partly inhibited. Taken together, these results show that NADPH oxidase ROS production is essential for complete activation of the main signalling pathways involved in megakaryocytopoiesis to occur. We suggest that this might also be important for in vivo megakaryocytopoiesis. Cell Death and Differentiation (2010) 17, 1842-1854; doi:10.1038/cdd.2010.67; published online 4 June 2010