Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family
Tissue mRNA expression of the rat UDP-glucuronosyltransferase gene family
复制标题
DOI：
10.1124/dmd.31.3.326
复制
发表时间：
2003-03-01
影响因子：
3.9
通讯作者：
Klaassen, CD
中科院分区：
文献类型：
--
作者：
Shelby, MK;Cherrington, NJ;Klaassen, CD
UDP-葡萄糖醛酸基转移酶（UGT）是II相生物转化酶，其葡萄糖醛酸化许多内源性和外源性底物。葡萄糖醛酸化增加底物的水溶性，并促进所得葡萄糖醛酸结合物的肾脏和胆汁排泄。UGT分为两个基因家族，UGT 1和UGT 2。尚未彻底检查UGT的组织分布，这些数据可以深入了解特定组织中单个UGT亚型的重要性以及UGT底物的药代动力学和靶器官毒性。因此，本研究的目的是测定大鼠UGT 1和UGT 2家族成员在肝脏、肾脏、肺、胃、十二指肠、空肠、回肠、大肠、小脑和大脑皮质以及鼻上皮中UGT 2A 1的mRNA水平。采用分支DNA信号放大分析检测UGT mRNA的组织水平。在许多组织中检测到三种UGT亚型，UGT 1A 1、UGT 1A 6和UGT 2B 12，而其他UGT亚型的分布更具组织特异性。例如，UGT 2A 1主要在鼻上皮中检测到。此外，UGT 1A 5、UGT 2B 1、UGT 2B 2、UGT 2B 3和UGT 2B 6主要在肝脏中检出。此外，UGT 1A 2、UGT 1A 3、UGT 1A 7和UGT 2B 8的检测对胃肠道（GI）具有一定的特异性。然而，并非所有这些UGT都在胃肠道的所有部分中检测到。UGT 1A 8的独特之处在于，在检查的任何组织中几乎都检测不到。总之，一些UGT亚型在多种组织中表达，而其他UGT亚型主要在某些组织中表达，如鼻上皮、肝脏或胃肠道。
UDP-Glucuronosyltransferases (UGTs) are phase II biotransformation enzymes that glucuronidate numerous endobiotic and xenobiotic substrates. Glucuronidation increases the water solubility of the substrate and facilitates renal and biliary excretion of the resulting glucuronide conjugate. UGTs have been divided into two gene families, UGT1 and UGT2. Tissue distribution of UGTs has not been thoroughly examined, and such data could provide insight into the importance of individual UGT isoforms in specific tissues and to the pharmacokinetics and target organ toxicity of UGT substrates. Therefore, the aim of this study was to determine mRNA levels of rat UGT1 and UGT2 family members in liver, kidney, lung, stomach, duodenum, jejunum, ileum, large intestine, cerebellum, and cerebral cortex, as well as nasal epithelium for UGT2A1. Tissue levels of UGT mRNA were detected using branched DNA signal amplification analysis. Three UGT isoforms, UGT1A1, UGT1A6, and UGT2B12, were detected in many tissues, whereas distribution of other UGT isoforms was more tissue-specific. For example, UGT2A1 was detected predominantly in nasal epithelium. Additionally, UGT1A5, UGT2B1, UGT2B2, UGT2B3, and UGT2B6 were detected primarily in liver. Furthermore, detection of UGT1A2, UGT1A3, UGT1A7, and UGT2B8 was somewhat specific to gastrointestinal (GI) tract. However, not all of these UGTs were detected in all portions of the GI tract. UGT1A8 was unique in that it was barely detectable in any of the tissues examined. In conclusion, some UGT isoforms were expressed in multiple tissues, whereas other UGT isoforms were predominantly expressed in a certain tissue such as nasal epithelium, liver, or GI tract.