Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Regular Article
Interpretation of the Effects of Protein Kinase C Inhibitors on Human UDP-glucuronosyltransferase 1A (UGT1A) Proteins in cellulo
Yuko ABERyoichi FUJIWARAShingo ODATsuyoshi YOKOIMiki NAKAJIMA
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2011 Volume 26 Issue 3 Pages 256-265

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Abstract

  UDP-glucuronosyltransferases (UGTs) catalyze the glucuronidation of a wide variety of xeno/endobiotics. Previous studies have reported that human UGT enzymes are phosphorylated and that treatment of cells with protein kinase C (PKC) inhibitors results in decreased UGT activities without affecting the UGT protein levels. In this study, we investigated the effects of PKC inhibitors on human UGT1A protein levels and activities in detail. When UGT1A-expressing HEK293 cells and LS180 cells were treated with curcumin or calphostin C, the exogenous and endogenous UGT1A protein levels in homogenates prepared with Tris-buffered saline were significantly decreased. Enzyme activity levels mirrored the changes in UGT protein levels. When the curcumin- or calphostin C-treated cells were lysed with buffer containing a detergent, the UGT protein levels did not decrease. We found that curcumin or calphostin C treatment facilitated the degradation of UGT protein after the cells were collected in the absence of a detergent. Finally, by in cellulo evaluation, we found that curcumin decreased UGT activity by the direct inhibitory effect, but calphostin C did not affect UGT activity. Thus, this study suggests that we should evaluate the data carefully when interpreting the effects of PKC inhibitors on UGT activity.

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© 2011 by The Japanese Society for the Study of Xenobiotics
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