title: Stereoselective characteristics and mechanisms of epidermal carboxylesterase metabolism observed in HaCaT keratinocytes.
abstract: 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.
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, 174 Chang-Hai Road, Shanghai 200433, PR China. qgzhu@126.com
authors.forename: Quan-Gang
authors.initials: QG
authors.lastname: Zhu
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Hu
authors.forename: Ji-Yong
authors.initials: JY
authors.lastname: Liu
authors.forename: Song-Wei
authors.initials: SW
authors.lastname: Lu
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Liu
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
mesh_terms: D043182:Carboxylesterase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004817:Epidermis / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology; D006801:Humans; D006868:Hydrolysis; D015603:Keratinocytes / Q000166:cytology / Q000201:enzymology*; D007660:Ketoprofen / Q000378:metabolism; D011355:Prodrugs / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D011355:Prodrugs; D012333:RNA, Messenger; D007660:Ketoprofen; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; C517204:CES2 protein, human; D043182:Carboxylesterase