Simultaneous expression of guinea pig UDP-glucuronosyltransferase 2B21 (UGT2B21) and 2B22 in COS-7 cells enhances UGT2B21-catalyzed chloramphenicol glucuronidation

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Yuji IshiiKazuta Oguri

Abstract

Our previous study suggested that hetero-oligomer formation of guinea pig liver UDP-glucuronosyltransferases (UGTs) 2B21 and 2B22 enhances UGT2B21-catalyzed morphine-6-glucuronidation. In this work, further evidence for a functional hetero-oligomer between UGT2B21 and UGT2B22 was provided by studies of the glucuronidation of chloramphenicol with dual expression in COS-7 cells. UGT2B21 expressed in COS cells was capable of glucuronidating the 3-hydroxyl group of morphine, 4-hydroxybiphenyl, borneol, testosterone, androsterone, and estriol, whereas it had some effect on chloramphenicol. On the contrary, UGT2B22 does not exhibit any significant activity toward these typical substrates tested in this study. When UGT2B21 and UGT2B22 were expressed simultaneously, the chloramphenicol glucuronidation was enhanced to 4.5-fold, whereas the activities toward other substrates were little affected except that for the 6-hydroxyl group of morphine. The protein expression level of UGT2B21 was comparable when UGT2B21 was expressed with or without UGT2B22. These results suggest that simultaneous expression of UGT2B21 and UGT2B22 enhances UGT2B21-catalyzed chloramphenicol glucuronidation. Hetero-oligomer formation of UGT2B21 and UGT2B22 may act ...Continue Reading

Citations

Oct 25, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yusuke OkadaHiroshi Yamazaki
Mar 3, 2011·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Hideo TakakusaSidney D Nelson
Jun 12, 2012·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Yasushi FujiokaNina Isoherranen
Jun 4, 2010·The Journal of Pharmacology and Experimental Therapeutics·Gloriane W SchnabolkDouglas H Sweet
Feb 16, 2006·American Journal of Physiology. Renal Physiology·Gloriane W SchnabolkDouglas H Sweet
Oct 13, 2009·Drug Metabolism Reviews·Yuji IshiiHideyuki Yamada
May 13, 2010·Drug Metabolism and Pharmacokinetics·Yuji IshiiHideyuki Yamada
Nov 9, 2016·Frontiers in Pharmacology·Ryoichi FujiwaraMiki Nakajima

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