Stereoselective characteristics and mechanisms of epidermal carboxylesterase metabolism observed in HaCaT keratinocytes.
Stereoselective characteristics and mechanisms of epidermal carboxylesterase metabolism observed in HaCaT keratinocytes.
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DOI：
10.1248/bpb.30.532
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发表时间：
2007-03
影响因子：
2
通讯作者：
Quan‐gang Zhu;Jin-hong Hu;Ji‐yong Liu;SongWei Lu;Yan-xia Liu;Jin Wang
中科院分区：
文献类型：
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作者：
Quan‐gang Zhu;Jin-hong Hu;Ji‐yong Liu;SongWei Lu;Yan-xia Liu;Jin Wang
越来越多的证据表明，表皮羧酸酯酶可能参与了前药经皮吸收的立体选择性水解。本研究旨在评估HaCaT角质形成细胞中表达的表皮羧酸酯酶水解酮洛芬乙酯的立体选择性特征和机制。酮洛芬乙酯主要被人HaCaT角质形成细胞的羧酸酯酶水解为r -酮洛芬。人羧酸酯酶-1 （hCE-1）和人羧酸酯酶-2 （hCE-2）在L02肝细胞中密集检测，hCE-2在HaCaT角化细胞中也密集检测，但hCE-1在HaCaT角化细胞中未检测到。因此，hCE-2在HaCaT角化细胞中是一种丰富的羧酸酯酶，它可能负责酮洛芬乙酯的立体选择性水解。
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.