Quantitative tissue and gene-specific differences and developmental changes in Nat1, Nat2, and Nat3 mRNA expression in the rat.
Quantitative tissue and gene-specific differences and developmental changes in Nat1, Nat2, and Nat3 mRNA expression in the rat.
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DOI：
10.1124/dmd.108.023564
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发表时间：
2008-12
期刊：
影响因子：
--
通讯作者：
Hein DW
中科院分区：
文献类型：
--
作者：
Barker DF;Walraven JM;Ristagno EH;Doll MA;States JC;Hein DW
人N-乙酰转移酶1(NAT1)和人N-乙酰转移酶2(NAT2)是参与外源生物生物转化的重要II相酶。在毒性和致癌性研究中，大鼠N-乙酰转移酶的功能多态性被认为是类似人类变异性的模型。为了准确定量这三种大鼠N-乙酰转移酶的表达，我们建立了对Nat1、Nat2和Nat3mRNAs的灵敏、特异的检测方法。在雄性F344大鼠中，Nat1(∼19倍)和Nat2(∼30倍)的组织特异性表达在有限的范围内变化，这两个基因在结肠中的表达最高。Nat3mRNA至少比Nat1或Nat2低两到三个数量级。比较雄性和雌性F344大鼠膀胱、结肠、肝脏和肺中Nat1和Nat2mRNA的表达，未发现显著的性别差异。在年龄从新生到成年的SpragueDawley和F344大鼠中，结肠在出生后的第一个月显示出Nat2增加了10倍，这与Nat1的变化没有相关性。相反，当Nat1略有增加时，Nat2在SpragueDawley或F344肝脏中没有表现出发育变化。这些对大鼠NAT表达的测量证实了Nat3的表达可以忽略不计，并且Nat1和Nat2是所有受试组织中芳香胺乙酰化活性的主要决定因素。这些发现证明了大鼠Nat1和Nat2基因的不同组织特异性和发育调节，并有助于更全面地了解人类和其他物种同源N-乙酰转移酶基因的组织特异性、性别特异性和发育特异性表达模式。
Human N-acetyltransferase 1 (NAT1) and 2 (NAT2) are important phase II enzymes involved in the biotransformation of xenobiotics. In toxicity and carcinogenicity studies, functional polymorphism of rat N-acetyltransferase is considered a model for similar human variability. To accurately quantitate expression of the three rat N-acetyltransferases, we developed sensitive, specific assays for Nat1, Nat2 and Nat3 mRNAs. In male F344 rats, tissue-specific expression varied over a limited range for both Nat1 (∼19-fold) and Nat2 (∼30-fold), with highest expression of both genes in colon. Nat3 mRNA was at least two to three orders of magnitude less than Nat1 or Nat2. Comparison of Nat1 and Nat2 mRNA expression in bladder, colon, liver and lung of male and female F344 rats detected no significant gender-specific difference. In Sprague Dawley and F344 rats ranging in age from neonate to mature adult, colon showed a >10-fold increase in Nat2 during the first postnatal month that did not correlate with changes in Nat1. In contrast, Nat2 showed no developmental change in Sprague Dawley or F344 liver as Nat1 increased modestly. These measures of rat Nat expression confirm that Nat3 expression is negligible and that Nat1 and Nat2 are the primary determinants of arylamine acetylation activity in all tested tissues. The findings demonstrate differential tissue-specific and developmental regulation of the rat Nat1 and Nat2 genes and contribute to more complete understanding of tissue-, gender-, and development-specific expression patterns of the cognate N-acetyltransferase genes of humans and other species.
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小鼠N-乙酰转移酶2型，人类N-乙酰转移酶类型1的同源物。
影响因子：
5.8
作者：
Kawamura, Akane;Westwood, Isaac;Wakefield, Larissa;Long, Hilary;Zhang, Naixia;Walters, Kylie;Redfield, Christina;Sim, Edith
通讯作者：
Sim, Edith
影响因子：
4.1
作者：
Boukouvala, S;Price, N;Sim, E
通讯作者：
Sim, E
影响因子：
3.9
作者：
Husain, Anwar;Zhang, Xiaoyan;Hein, David W.
通讯作者：
Hein, David W.
影响因子：
3.8
作者：
McQueen, CA;Chau, B
通讯作者：
Chau, B
影响因子：
3.9
作者：
Sugamori, K. S.;Brenneman, D.;Grant, D. M.
通讯作者：
Grant, D. M.