UDP-glucuronosyltransferase in the rat olfactory bulb: Identification of the UGT1A6 isoform and age-related changes in 1-naphthol glucuronidation

被引:13
作者
Gradinaru, D
Suleman, FG
Leclerc, S
Heydel, JM
Grillasca, JP
Magdalou, J
Minn, A
机构
[1] Univ Henri Poincare, CNRS, UMR 7561,Fac Med, Pharmacol Lab, F-54505 Vandoeuvre Les Nancy, France
[2] Natl Inst Gerontol & Geriatr Ana Aslan, Bucharest 78178, Romania
[3] Fac Pharm, Lab Biochim Pharmacol, F-21033 Dijon, France
关键词
drug metabolism; glucuronidation; olfactory bulb; neurotoxicity; aging; blood-brain barrier;
D O I
10.1023/A:1021048525012
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Xenobiotic glucuronidation represents a major metabolic protection of the brain against chemical aggressions at blood-brain interfaces. We previously observed that glucuronidation of l-naphthol was very effective in olfactory bulb, which is a pathway for the entry of foreign molecules into the brain. In this wort;, we showed that l-naphthol glucuronidation varied according to age. It was very high at birth, then decreased markedly in 3-month-old rats and increased again significantly during aging. By Western blot and reverse transcription-polymerase chain reaction (RT-PCR), we demonstrated the presence in the olfactory bulb of the UDP-glucuronosyltransferase (UGT) 1A6 isoform, which catalyzes the glucuronidation of phenols, such as l-naphthol. Quantitative RT-PCR indicated that the mRNA levels encoding UGT1A6 did not significantly change according to age, thus suggesting that other differently regulated UGT isoforms were present and would account for the variations of l-naphthol glucuronidation observed.
引用
收藏
页码:995 / 1000
页数:6
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