Marked increases in hepatic NAD(P)H:oxidoreductase gene transcription and mRNA levels correlated with a mouse chromosome 7 deletion.
Marked increases in hepatic NAD(P)H:oxidoreductase gene transcription and mRNA levels correlated with a mouse chromosome 7 deletion.
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肝脏 NAD(P)H:氧化还原酶基因转录和 mRNA 水平显着增加与小鼠 7 号染色体缺失相关。
DOI：
10.1073/pnas.86.17.6699
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发表时间：
1989
影响因子：
11.1
通讯作者：
D. Nebert
中科院分区：
文献类型：
--
作者：
Daniel D. Petersen;Frank J. Gonzalez;Vesna Rapic;Christine A. Kozak;Jong;John E. Jones;D. Nebert
NAD（P）H：甲萘醌氧化还原酶基因（Nmo-1）编码醌还原酶（也称为DT黄递酶; EC 1.6.99.2），据信其在保护免受氧化应激中起核心作用。我们研究了辐射诱导染色体缺失的小鼠，涉及7号染色体上的白化病位点（c），发现与未处理的Cch/Cch野生型和Cch/C14 CoS杂合子相比，未处理的c14 CoS/c14 CoS缺失纯合子中的Nmo-1 mRNA水平和Nmo-1基因转录速率显著增加（分别大于100倍和大于12倍）。这些数据表明，位于7号染色体上的基因编码一个反式调节因子，可能是Nmo-1基因的负效应子，我们在这里显示，它位于8号染色体上，距离Es-2基因约1.4厘摩（约1000个酶对）。相反，没有可检测的细胞色素P1450（Cyp 1a 1基因）或细胞色素P3450（Cyp 1a 2基因）mRNA的基础水平，表明Cyp 1a 1和Cyp 1a 2基因的基础表达的调节与Nmo-1基因不同。此外，Cyp 1a 1和Cyp 1a 2基因和Nmo-1基因在cch/cch、cch/c14 CoS和c14 CoS/c14 CoS小鼠中被四氯二苯并对二恶英诱导。因此，四氯二苯并-对-二恶英诱导Cyp 1a 1、Cyp 1a 2和Nmo-1基因的机制独立于未治疗的c14 CoS/c14 CoS小鼠中Nmo-1基因激活的机制。
The NAD(P)H:menadione oxidoreductase gene (Nmo-1) codes for a quinone reductase (also called DT diaphorase; EC 1.6.99.2) believed to play a central role in protection against oxidative stress. We have studied mice with a radiation-induced chromosomal deletion involving the albino locus (c) on chromosome 7 and found that Nmo-1 mRNA levels and the rate of Nmo-1 gene transcription are markedly increased (greater than 100-fold and greater than 12-fold, respectively) in the untreated c14CoS/c14CoS deletion homozygote, compared with the untreated Cch/Cch wild-type and the Cch/C14CoS heterozygote. These data suggest that a gene located on chromosome 7 encodes a trans-acting regulatory factor that might be a negative effector of the Nmo-1 gene, which we show here is located on chromosome 8 approximately 1.4 centimorgans (about 1000 kilobase pairs) from the Es-2 gene. Conversely, there are no detectable basal levels of cytochrome P1450 (Cyp1a1 gene) or cytochrome P3450 (Cyp1a2 gene) mRNA, indicating that the regulation of basal expression of the Cyp1a1 and Cyp1a2 genes is distinct from that of the Nmo-1 gene. Moreover, the Cyp1a1 and Cyp1a2 genes and the Nmo-1 gene are induced by tetrachlorodibenzo-p-dioxin in the cch/cch, cch/c14CoS, and c14CoS/c14CoS mice. The mechanism of tetrachlorodibenzo-p-dioxin inducibility of the Cyp1a1, Cyp1a2, and Nmo-1 genes is, therefore, independent of the mechanism of Nmo-1 gene activation in untreated c14CoS/c14CoS mice.