Relationship between Radiosensitivity and Nrf2 Target Gene Expression in Human Hematopoietic Stem Cells
Relationship between Radiosensitivity and Nrf2 Target Gene Expression in Human Hematopoietic Stem Cells
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DOI：
10.1667/rr2146.1
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发表时间：
2010-08-01
影响因子：
3.4
通讯作者：
Kashiwakura, Ikuo
中科院分区：
文献类型：
--
作者：
Kato, Kengo;Takahashi, Kenji;Kashiwakura, Ikuo
NFE2相关因子2（Nrf2）属于碱性区域亮氨酸拉链转录因子的帽“n”领家族，是多种抗氧化基因表达协同转录诱导中的关键蛋白。本研究的目的是分析从人胎盘/脐带血造血干细胞（HSCs）制备的CD34(+)细胞经X射线照射后，Nrf2靶基因如血红素加氧酶1（HO - 1）、铁蛋白重链多肽1（FTH1）、NAD(P)H脱氢酶（醌1）（NQO1）、谷氨酸 - 半胱氨酸连接酶催化亚基、谷氨酸 - 半胱氨酸连接酶修饰亚基、谷胱甘肽还原酶（GSR）和硫氧还蛋白还原酶1（TXNRD1）的表达情况。我们评估了造血干细胞的放射敏感性与Nrf2靶基因表达之间的关系。经2戈瑞照射的造血干细胞来源的集落形成细胞数量减少至未照射对照的约20%。同时，X射线照射后HO - 1、FTH1、NQO1、GSR和TXNRD1的mRNA表达显著增加。在造血干细胞的存活分数与固有NQO1 mRNA表达之间观察到具有统计学意义的负相关，这表明NQO1 mRNA水平较低的造血干细胞可能也具有放射抗性。目前的结果表明与Nrf2相关的抗氧化系统参与了造血干细胞的放射敏感性。（C）2010年，辐射研究学会
NFE2-related factor 2 (Nrf2), which belongs to the cap "n" collar family of basic region leucine zipper transcription factors, is a key protein in the coordinated transcriptional induction of expression of various antioxidant genes. The purpose of this study was to analyze the expression of Nrf2 target genes, such as heme oxygenase 1 (HO-1), ferritin heavy polypeptide 1 (FTH1), NAD(P)H dehydrogenase, quinone 1 (NQO1), glutamate-cysteine ligase catalytic subunit, glutamate-cysteine ligase modifier subunit, glutathione reductase (GSR) and thioredoxin reductase 1 (TXNRD1), after X irradiation of CD34(+) cells that were prepared from human placental/umbilical cord blood hematopoietic stem cells (HSCs). We evaluated the relationship between radiosensitivity and expression of Nrf2 target genes in HSCs. The number of colony-forming cells derived from 2-Gy-irradiated HSCs decreased to approximately 20% of the nonirradiated control. At the same time, the mRNA expression of HO-1, FTH1, NQO1, GSR and TXNRD1 was significantly increased after X irradiation. A statistically significant negative correlation was observed between the surviving fraction of HSCs and the intrinsic NQO1 mRNA expression, indicating that HSCs in which NQO1 mRNA levels are low may also be radioresistant. The present results suggest that the antioxidant system associated with Nrf2 is involved in the radiosensitivity of HSCs. (C) 2010 by Radiation Research Society