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.
journal_name
Drug Metab Pharmacokinetjournal_title
Drug metabolism and pharmacokineticsauthors
Abe Y,Fujiwara R,Oda S,Yokoi T,Nakajima Mdoi
10.2133/dmpk.DMPK-10-RG-121subject
Has Abstractpub_date
2011-06-01 00:00:00pages
256-65issue
3eissn
1347-4367issn
1880-0920pii
JST.JSTAGE/dmpk/DMPK-10-RG-121journal_volume
26pub_type
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