Monospecific Antipeptide Antibodies Against Human Hepatic UDP-Glucuronosyltransferase 1A Subfamily (UGT1A) Isoforms

Summary:Expression of UDP-glucuronosyltransferases (UGT) in mammals is thought to be regulated in both a tissue- and developmental-specific manner. Furthermore, induction of genes encoding UGT occurs after exposure to xenobiotics including drugs, environmental pollutants and dietary compounds. In human, isoforms of UGT 1A subfamily catalyze the glucuronidation of a greater proportion of drugs, suggesting that the expression of UGT1A isoforms is responsible for the clearance of a diverse range of drugs. To analyze the expression of human UGT1A isoforms, we have developed polyclonal antibodies against specific peptide regions within the isoforms (UGT1A1, 1A3, 1A4, 1A6 and 1A9). The prepared antipeptide antibodies were found to be highly monospecific for each UGT1A isoform and no crossreactivity with UGT2B isoforms was detected. Analysis of UGT1A protein levels in hepatic microsomes using these antibodies demonstrated interindividual differential expression of each isoform. These highly specific antipeptide antibodies provide an important tool to analyze tissue distribution and interindividual expression levels of human UGT1As.