Stereoselective Characteristics and Mechanisms of Epidermal Carboxylesterase Metabolism Observed in HaCaT Keratinocytes

There is increasing evidence that epidermal carboxylesterase may be involved in the stereoselective hydrolysis of prodrugs in percutaneous absorption. The present study was designed to evaluate the stereoselective characteristics and mechanisms of ketoprofen ethyl ester hydrolysis by epidermal carbo...

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Bibliographic Details
Published in:Biological & Pharmaceutical Bulletin 2007, Vol.30(3), pp.532-536
Main Authors: Zhu, Quan-Gang, Hu, Jin-Hong, Liu, Ji-Yong, Lu, Song-Wei, Liu, Yan-Xia, Wang, Jin
Format: Article
Language:English
Subjects:
Carboxylesterase - chemistry
Carboxylesterase - genetics
Carboxylesterase - metabolism
Carboxylic Ester Hydrolases - chemistry
Carboxylic Ester Hydrolases - genetics
Carboxylic Ester Hydrolases - metabolism
Cell Line
Chromatography, High Pressure Liquid
Epidermis - enzymology
Gene Expression Regulation, Enzymologic
HaCaT keratinocyte
Hepatocytes - cytology
Hepatocytes - enzymology
human carboxylesterase
Humans
Hydrolysis
Keratinocytes - cytology
Keratinocytes - enzymology
Ketoprofen - metabolism
ketoprofen ethyl ester
Prodrugs - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
Stereoisomerism
stereoselectivity
Substrate Specificity
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Summary:There is increasing evidence that epidermal carboxylesterase may be involved in the stereoselective hydrolysis of prodrugs in percutaneous absorption. The present study was designed to evaluate the stereoselective characteristics and mechanisms of ketoprofen ethyl ester hydrolysis by epidermal carboxylesterase expressed in HaCaT keratinocytes. Ketoprofen ethyl ester was mainly hydrolyzed to R-ketoprofen by carboxylesterase of human HaCaT keratinocytes. Human carboxylesterase-1 (hCE-1) and human carboxylesterase-2 (hCE-2) were intensively detected in L02 hepatocytes, hCE-2 was also intensively detected in HaCaT keratinocytes, but hCE-1 was not detected in HaCaT keratinocytes. hCE-2 is thus an abundant carboxylesterase in HaCaT keratinocytes which may be responsible for stereoselective hydrolysis of ketoprofen ethyl ester.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.30.532