Role of the plasma membrane ROS-generating NADPH oxidase in CD34+ progenitor cells preservation by hypoxia
Role of the plasma membrane ROS-generating NADPH oxidase in CD34+ progenitor cells preservation by hypoxia
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DOI：
10.1016/j.jbiotec.2007.05.023
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发表时间：
2007-07-15
影响因子：
4.1
通讯作者：
Tan, Wen-Song
中科院分区：
文献类型：
--
作者：
Fan, Jinli;Cai, Haibo;Tan, Wen-Song
缺氧有利于骨髓造血干细胞和祖细胞（HSPCs）祖细胞特性的保存。本工作旨在研究缺氧对体外培养的脐血CD 34（+）细胞中产生活性氧（ROS）的NADPH氧化酶系统的调节作用。结果表明，相对于正常氧张力，缺氧时NADPH氧化酶活性和ROS产生减少。NADPH氧化酶抑制剂二苯基碘鎓和活性氧清除剂N-乙酰半胱氨酸均能抑制活性氧的产生。缺氧时NADPH氧化酶mRNA和p67蛋白水平相应降低。对祖细胞特征的分析，包括表达HSPC标记物CD 34（+）CD 38（-）的培养细胞的比例、集落形成细胞（CFC）的集落产生能力和培养的CD 34（+）细胞的再扩增能力，显示5%pO（2）或减少的ROS有利于保留CD 34（+）祖细胞的特征，并促进CD 34（+）CD 38（-）细胞的扩增。以上结果表明，缺氧通过调节NADPH氧化酶保持较低的细胞内活性氧水平，有效地维持了CD 34（+）细胞的生物学特性。(c)2007 Elsevier B. V.保留所有权利。
Hypoxia favored the preservation of progenitor characteristics of hematopoietic stem and progenitor cells (HSPCs) in bone marrow. This work aimed at studying the role of reactive oxygen species (ROS)-generating NADPH oxidase system regulated by hypoxia in ex vivo cultures of cord blood CD34(+) cells. The results showed that NADPH oxidase activity and ROS generation were reduced in hypoxia with respect to normal oxygen tension. Meanwhile the ROS generation was found to be inhibited by diphenyleneiodonium (the NADPH oxidase inhibitor), or N-acetylcysteine (the ROS scavenger). Accordingly NADPH oxidase mRNA and p67 protein levels decreased in hypoxia. The analysis of progenitor characteristics, including the proportion of cultured cells expressing the HSPCs marker CD34(+)CD38(-), colony production ability of the colony-forming cells (CFCs), and the re-expansion capability of the cultured CD34(+) cells, showed that either 5% pO(2) or reduced ROS favored preserving the characteristics of CD34(+) progenitors, and promoted the expansion of CD34(+)CD38(-) cells as well. The above results demonstrated that hypoxia effectively maintained biological characteristics of CD34(+) cells through keeping lower intracellular ROS levels by regulating NADPH oxidase. (c) 2007 Elsevier B.V. All rights reserved.