Biochemical and Biophysical Research Communications
Ontogenic isoform switching of UDP–glucuronosyltransferase family 1 in rat liver
Section snippets
Rat liver samples
Fetal rat livers were obtained from timed-pregnant rats, and they were obtained from Nihon SLC inc. (Shizuoka, Japan). Male Wistar rats were used in this study except for 16-day-fetuses, which cannot be distinguished by morphological sex differences. Livers were excised from rats, cut into pieces with scissors, and then quickly frozen in liquid nitrogen. For each age analyzed, a total of six to nine rat livers were pooled before use.
Preparation of total RNA and analysis of mRNA expression
Frozen liver samples (0.2 g) were crushed with a glass morter
Ontogenic expression profiles and switching of UGT1 mRNA
Our previous studies determined the genomic organization of the rat UGT1 gene complex and demonstrated drug-responsive and tissue-specific expression of each UGT1 isoform [6]. The N-terminal substrate-binding domains of each UGT1 isoform are encoded by distinct large first exons, while the C-terminal UDP-glucuronic acid-binding domain of all UGT1 isoforms is identical and is encoded by four commonly used exons (Fig. 1). The isoform-specific first exons are organized in a tandem array, and the
Concluding remarks
We have demonstrated that the UGT1A1 gene is silenced before birth while the UGT1A6 gene is active in the developing rat liver. The perinatal isoform switching, that is a shift from phenol-glucuronidating UGT1A6 to bilirubin-metabolizing UGT1A1, in hepatic microsomes occurred after birth. This transition period between fetus and neonate is linked to the inadequacy of perinatal glucuronidation of bilirubin and the common etiology of idiopathic hyperbilirubinemia in the newborn infant. We also
Acknowledgments
This work was supported in part by the Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan and Grants for Scientific Research from the Foundation of Himeji Institute of Technology.
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