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Cloning and Expression of Human UDP-Glucuronosyltransferase (UGT) 1A8

https://doi.org/10.1006/abbi.1998.0781Get rights and content

Abstract

The mRNA expression of human UDP-glucuronosyltransferase 1A8 (UGT1A8) has been found in jejunum, ileum, and colon but not in liver. A cDNA with a complete UGT1A8 coding region was amplified from total human ileal RNA by reverse transcriptase–polymerase chain reaction and inserted into the mammalian expression vector, pcDNA3. Lysates of HK293 cells expressing UGT1A8 revealed the expression of a protein with a molecular mass of 56 kDa by Western blot analysis. Transiently expressed human UGT1A8 shows glucuronidation activities with coumarins, anthraquinones, flavonoids, phenolic compounds, catechol estrogens, 17-hydroxyandrogens, primary amines such as the carcinogen 4-aminobiphenyl, and certain opioids. This UGT may play an important role in the detoxification of xenobiotics in human intestine.

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      UGT1A3 metabolizes some endogenous compounds such as estrone, 2-hydroxyestradiol and 2-hydroxyestrone (Radominska-Pandya et al., 1999). UGT1A8 and UGT1A10 are involved in the glucuronidation of several steroids (Cheng et al., 1998, 1999). UGT1A9 glucuronidates the thyroid hormones, thyroxine and reverse triiodothyronine (Visser et al., 1993).

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    This research was supported by National Institutes of Health Grants GM26221 (T.R.T.) and DK-45123 and DK-49715 (A.R-P.).

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    To whom correspondence should be addressed at Department of Pharmacology, 2-452 Bowen Science Building, The University of Iowa, Iowa City, IA 52242. Fax: (319) 335-8930.

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