Abstract
Rat liver recombinant BR1UGT1.1 was found to have significant activity toward retinoid substrates. UGT1.1 glucuronidation activity was 91 ± 18 pmol/mg × min for atRA and 113 ± 19 pmol/mg × min for 5,6-epoxy-atRA. The apparentKM and Vmax of atRA acid glucuronidation by UGT1.1 were 59.1 ± 5.4 μM and 158 ± 43 pmol/mg × min, respectively. SDS-PAGE and Western blot analysis of UGT1.1-transfected HK293 membrane proteins photolabeled with [11,12-3H]atRA revealed a protein of ∼56 kDa that was labeled by [3H]atRA, detected by anti-pNP UGT antibody and not present in membranes from nontransfected HK293 cells. Liver microsomes from Gunn rats, which lack UGT1.1, had significant activity toward atRA (111 ± 28 pmol/mg × min).
Footnotes
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Send reprint requests to: Dr. Anna Radominska, Division of Gastroenterology, University of Arkansas for Medical Science, 4301 West Markham, Slot 567, Little Rock, AR 72205.
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This work was supported in part by Grants DK45123 and DK49715 (to A.R.), GM26221 (to T.R.T.), and ES06765 (V.S.) from the National Institutes of Health.
- Abbreviations used are::
- BR
- bilirubin
- UGT
- UDP-glucuronosyltransferase
- atRA
- all-trans-retinoic acid
- 5
- 6-epoxy-atRA, 5,6-epoxy-all-trans-retinoic acid
- SDS-PAGE
- sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- pNP
- 4-nitrophenol
- UDP-GlcUA
- UDP-glucuronic acid
- SD
- Sprague-Dawley
- BSA
- bovine serum albumin
- RA
- retinoic acid
- RLM
- rat liver microsome
- Received January 16, 1997.
- Accepted March 26, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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