Yang_2009_Biochem.Pharmacol_77_238

Reference

Title : Human carboxylesterases HCE1 and HCE2: ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin - Yang_2009_Biochem.Pharmacol_77_238
Author(s) : Yang D , Pearce RE , Wang X , Gaedigk R , Wan YJ , Yan B
Ref : Biochemical Pharmacology , 77 :238 , 2009
Abstract : Carboxylesterases hydrolyze chemicals containing such functional groups as a carboxylic acid ester, amide and thioester. The liver contains the highest carboxylesterase activity and expresses two major carboxylesterases: HCE1 and HCE2. In this study, we analyzed 104 individual liver samples for the expression patterns of both carboxylesterases. These samples were divided into three age groups: adults (>or= 18 years of age), children (0 days-10 years) and fetuses (82-224 gestation days). In general, the adult group expressed significantly higher HCE1 and HCE2 than the child group, which expressed significantly higher than the fetal group. The age-related expression was confirmed by RT-qPCR and Western immunoblotting. To determine whether the expression patterns reflected the hydrolytic activity, liver microsomes were pooled from each group and tested for the hydrolysis of drugs such as oseltamivir and insecticides such as deltamethrin. Consistent with the expression patterns, adult microsomes were approximately 4 times as active as child microsomes and 10 times as active as fetal microsomes in hydrolyzing these chemicals. Within the same age group, particularly in the fetal and child groups, a large inter-individual variability was detected in mRNA (430-fold), protein (100-fold) and hydrolytic activity (127-fold). Carboxylesterases are recognized to play critical roles in drug metabolism and insecticide detoxication. The findings on the large variability among different age groups or even within the same age group have important pharmacological and toxicological implications, particularly in relation to pharmacokinetic alterations of ester drugs in children and vulnerability of fetuses and children to pyrethroid insecticides.
ESTHER : Yang_2009_Biochem.Pharmacol_77_238
PubMedSearch : Yang_2009_Biochem.Pharmacol_77_238
PubMedID: 18983829
Gene_locus related to this paper: human-CES1 , human-CES2

Related information

Gene_locus related to this paper: human-CES1 , human-CES2

Citations formats

Yang D, Pearce RE, Wang X, Gaedigk R, Wan YJ, Yan B (2009)
Human carboxylesterases HCE1 and HCE2: ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin
Biochemical Pharmacology 77 :238

Yang D, Pearce RE, Wang X, Gaedigk R, Wan YJ, Yan B (2009)
Biochemical Pharmacology 77 :238