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UGT1家族的尿苷二磷酸葡萄糖醛酸转移酶在人肝脏和肾脏中的表达以及对药物的反应。

The expression of UDP-glucuronosyltransferases of the UGT1 family in human liver and kidney and in response to drugs.

作者信息

Sutherland L, Ebner T, Burchell B

机构信息

Department of Biochemical Medicine, Ninewells Hospital and Medical School, University of Dundee, U.K.

出版信息

Biochem Pharmacol. 1993 Jan 26;45(2):295-301. doi: 10.1016/0006-2952(93)90064-4.

DOI:10.1016/0006-2952(93)90064-4
PMID:8435089
Abstract

The expression of human UDP-glucuronosyltransferase (UGT) 1 gene family in the liver and kidney was examined using specific enzyme activity, antibodies and DNA probes for each of the four family members. Phenol UGT HP1 was expressed at a similar, relatively low, abundance in each liver and kidney whereas phenol UGT HP4 was more highly expressed in the kidney. Bilirubin UGTs (HP2 and HP3) were not detectable in the kidney and HP3 was the major isoform in the liver. The UGT activities towards certain specific substrates correlated well with the respective mRNA levels in the tissues. Bilirubin UGT HP3 was induced 2-3-fold in the livers from patients treated with phenytoin and phenobarbital. Storage of a human liver in University of Wisconsin solution which contains dexamethasone and insulin caused a large accumulation of all the UGT mRNAs, but these were not quantitatively translated into expressed UGT activities. The implications of these results are discussed.

摘要

使用针对四个家族成员各自的特异性酶活性、抗体和DNA探针,检测了人尿苷二磷酸葡萄糖醛酸基转移酶(UGT)1基因家族在肝脏和肾脏中的表达。苯酚UGT HP1在肝脏和肾脏中的表达丰度相似且相对较低,而苯酚UGT HP4在肾脏中的表达更高。胆红素UGT(HP2和HP3)在肾脏中无法检测到,HP3是肝脏中的主要同工型。对某些特定底物的UGT活性与组织中各自的mRNA水平密切相关。在用苯妥英和苯巴比妥治疗的患者肝脏中,胆红素UGT HP3被诱导了2至3倍。将人肝脏储存在含有地塞米松和胰岛素的威斯康星大学溶液中,会导致所有UGT mRNA大量积累,但这些并未定量转化为表达的UGT活性。讨论了这些结果的意义。

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