Expression of UGT1A and UGT2B mRNA in Human Normal Tissues and Various Cell Lines

Abstract

ABSTRACT:UDP-glucuronosyltransferases (UGTs) are major phase II drug metabolism enzymes that catalyze the glucuronidation of numerous endogenous and exogenous compounds. UGTs are divided into two families, UGT1 and UGT2, based on evolutionary divergence and homology. Nine UGT1A and seven UGT2B functional isoforms have been identified in humans. Glucuronidation occurs mainly in liver but also in various extrahepatic tissues, possibly affecting the pharmacokinetics. In the present study, we comprehensively determined the expression of all functional UGT1A and UGT2B isoforms in normal human tissues including liver, lung, stomach, small intestine, colon, kidney, bladder, adrenal gland, breast, ovary, uterus, and testis by semiquantitative reverse transcription-polymerase chain reaction. In addition, the expressions of these UGTs mRNA in 15 kinds of human tissue-derived cell lines were also analyzed. Many UGT isoforms were abundantly expressed in the liver, gastrointestinal tract, and kidney, supporting previous studies. Interestingly, we found that all UGTs except UGT2B17 were expressed in bladder. In steroidrelated tissues, UGTs were expressed in tissue-and isoform-specific manners. Expression profiles in human tissue-derived cell lines were not necessarily consistent with those in corresponding normal tissues. Different expression profiles were observed in distinct cell lines derived from the same organ. The information presented here will be helpful for understanding the glucuronidation in various tissues and for choosing appropriate cell lines for in vitro studies.

Dopamine Is a Low-Affinity and High-Specificity Substrate for the Human UDP-Glucuronosyltransferase 1A10

“…UGT1A10 was considered an extrahepatic UGT that is mainly expressed in the intestine (Strassburg et al, 1997(Strassburg et al, , 1998(Strassburg et al, , 1999Mojarrabi and Mackenzie, 1998;Cheng et al, 1999;Zheng et al, 2002). However, in a recent study, low expression levels of UGT1A10 were detected in liver and hepatocytes (Li et al, 2007;Nakamura et al, 2008). Based on the latter, it might be speculated that low expression levels of UGT1A10 that were not detected previously could also occur in the brain.…”

Increased UGT1A3 and UGT1A7 Expression is Associated with Pancreatic Cancer

“…In addition to genetic polymorphism, the induction by environmental and/or diet would be casual factors of the variability of the UGT expression (Nakamura et al, 2008). Moreover, it was shown that UGT expression was restricted to certain cell types or regions in an organ by immunohistochemical studies.…”

Gene expression of peripheral blood lymphocytes may discriminate patients with schizophrenia from controls

“…Although it is important to stress that a larger and independent group, which includes women with schizophrenia, must be tested, we have chosen the male gender due to the possible confounding of female hormonal states at the time of blood sampling and the effect of contraceptives, which influence on the gene expression profiles (Nakamura et al, 2008). Besides, we used a customised microarray platform, with enrichment for neurodevelopment genes, due to their involvement with the disease (Palha and Goodman, 2006;Ruano et al, 2008) and the current accepted view that schizophrenia is a neurodevelopment disorder in which genes and environment interplay for disease onset and progression.…”