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 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.
Zhu
Quan-Gang
QG
Department of Pharmacy, Changhai Hospital, Second Military Medical University, 174 Chang-Hai Road, Shanghai 200433, PR China. qgzhu@126.com
Hu
Jin-Hong
JH
Liu
Ji-Yong
JY
Lu
Song-Wei
SW
Liu
Yan-Xia
YX
Wang
Jin
J
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
D011355:Prodrugs; D012333:RNA, Messenger; D007660:Ketoprofen; D002265:Carboxylic Ester Hydrolases; C474609:CES1 protein, human; C517204:CES2 protein, human; D043182:Carboxylesterase