Placental profiling of UGT1A enzyme expression and activity and interactions with preeclampsia at term

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• 作者：Abby C. Collier ; Audrey D. Thévenon…
• 关键词：Developmental pharmacology ; Glucuronidation ; Obstetrics ; Phase II metabolism
• 刊名：European Journal of Drug Metabolism and Pharmacokinetics
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：40
• 期：4
• 页码：471-480
• 全文大小：739 KB
• 参考文献：Ashida H, Nishiumi S, Fukuda I (2008) An update on the dietary ligands of the AhR. Exp Opin Drug Metab Toxicol 4:1429-447CrossRef
  Barbier O, Girard C, Breton R, Belanger A, Hum DW (2000) N-glycosylation and residue 96 are involved in the functional properties of UDP-glucuronosyltransferase enzymes. Biochemistry 39:11540-1552CrossRef PubMed
  Basu NK, Kole L, Basu M, Chakraborty K, Mitra PS, Owens IS (2008) The major chemical-detoxifying system of UDP-glucuronosyltransferases requires regulated phosphorylation supported by protein kinase C. J Biol Chem 283:23048-3061PubMedCentral CrossRef PubMed
  Benirschke K, Kaufmann P, Baergen RN (2006) Pathology of the human placenta, 5th edn. Springer, Amsterdam
  Bock KW (2010) Functions and transcriptional regulation of adult human hepatic UDP-glucuronosyl-transferases (UGTs): mechanisms responsible for interindividual variation of UGT levels. Biochem Pharmacol 80:771-77CrossRef PubMed
  Buckley DB, Klaassen CD (2007) Tissue- and gender-specific mRNA expression of UDP-glucuronosyltransferases (UGTs) in mice. Drug Metab Dispos 35:121-27CrossRef PubMed
  Buckley DB, Klaassen CD (2009) Mechanism of gender-divergent UDP-glucuronosyltransferase mRNA expression in mouse liver and kidney. Drug Metab Dispos 37:834-40PubMedCentral CrossRef PubMed
  Burchell B, Coughtrie M, Jackson M, Harding D, Fournel-Gigleux S, Leakey J, Hume R (1989) Development of human liver UDP-glucuronosyltransferases. Dev Pharmacol Ther 13:70-7PubMed
  Collier A, Tingle M, Keelan J, Paxton J, Mitchell M (2000) A highly sensitive fluorescent microplate method for the determination of UDP-glucuronosyl transferase activity in tissues and placental cell lines. Drug Metab Dispos 28:1184-186PubMed
  Collier A, Ganley N, Tingle M, Blumenstein M, Marvin K, Paxton J, Mitchell M, Keelan J (2002a) UDP-glucuronosyltransferase activity, expression and cellular localization in human placenta at term. Biochem Pharmacol 63:409-19CrossRef PubMed
  Collier A, Tingle M, Paxton J, Mitchell M, Keelan J (2002b) Metabolizing enzyme localization and activities in the first trimester human placenta: the effect of maternal and gestational age, smoking and alcohol consumption. Hum Reprod 17:2564-572CrossRef PubMed
  Collier A, Keelan J, Zijl PV, Paxton J, Mitchell M, Tingle M (2004) Human placental glucuronidation and transport of 3-azido-3-deoxythymidine (AZT) and uridine diphosphate glucuronic acid (UDPGA). Drug Metab Dispos 32:813-20CrossRef PubMed
  Collier AC, Miyagi SJ, Yamauchi Y, Ward MA (2009) Assisted reproduction technologies impair placental steroid metabolism. J Steroid Biochem Mol Biol 116:21-8PubMedCentral CrossRef PubMed
  Collier A, Milam KA, Rougée LR, Sugawara A, Yamauchi Y, Ward MA (2012) Upregulation of Ugt1a genes in placentas and fetal livers in a murine model of assisted reproduction. Placenta 33:77-0PubMedCentral CrossRef PubMed
  Congiu M, Mashford M, Slavin J, Desmond PD (2002) UDP glucuronosyltransferase mRNA levels in human liver disease. Drug Metab Dispos 30:129-34CrossRef PubMed
  Coughtrie MW, Burchell B, Leakey JE, Hume R (1988) The inadequacy of perinatal glucuronidation: immunoblot analysis of the developmental expression of individual UDP-glucuronosyltransferase isoenzymes in rat and human liver microsomes. Mol Pharmacol 34:729-35PubMed
  Court M, Greenblatt DJ (1997) Molecular basis for deficient acetaminophen glucuronidation in cats. An interspecies comparison of enzyme kinetics in liver microsomes. Biochem Pharmacol 53:1041-041CrossRef PubMed
  Court M, Greenblatt DJ (2000) Molecular genetic basis for deficient acetaminophen glucuronidation by cats: UGT1A6 is a pseudogene, and evidence for reduced diversity of expressed hepatic UGT1A isoforms. Pharmacogenetics 10:355-69CrossRef PubMed
  Court MH, Zhang X, Ding X, Yee KK, Hesse LM, Finel M (2011) Quantitative distribution of mRNAs encoding the 19 human UDP-glucuronosyltransferase enzymes in 26 adult and 3 fetal tissues. Xenobiotica 42:266-77CrossRef PubMed
  Divakaran K, Hines RN, McCarver DG (2014) Human hepatic UGT2B15 developmental expression. Toxicol Sci 141:292-99PubMedCentral CrossRef PubMed
  Duckitt K, Harrington D (2005) Risk factors for pre-eclampsia at antenatal booking: systematic review of controlled studies. BMJ 330:565PubMedCentral CrossRef PubMed
  Fajardy I, Moitrot E, Vambergue A, Vandersippe-Millot M, Deruelle P, Rousseaux J (2009) Time course analysis of RNA stability in human placenta. BMC Mol Biol 10:21PubMedCentral CrossRef PubMed
  Finel M, Li X, Gardner-Stephen D, Bratton S, Mackenzie PI, Radominska-Pandya A (2005) Human UDP-glucuronosyltransferase 1A5: identification, expression, and activity. J Pharmacol Exp Ther 315:1143-149CrossRef PubMed
  Fyffe J, Dutton GJ (1975) Induction of UDP glucose dehydrogenase during development, organ culture, and exposure to phenobarbital. Its relation to levels of UDP glucuronic acid and overall glucuronidation in
• 作者单位：Abby C. Collier (1) (2)
  Audrey D. Thévenon (1)
  William Goh (3)
  Mark Hiraoka (3)
  Claire E. Kendal-Wright (3) (4)
  
  1. Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI, 96813, USA
  2. Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC, V6T 1Z3, Canada
  3. Department of Obstetrics, Gynecology and Women’s Health, John A. Burns School of Medicine, Kapi‘olani Medical Center for Women and Children, 1319 Punahou Street, Honolulu, HI, 96826, USA
  4. Division of Natural Sciences and Mathematics, Chaminade University of Honolulu, 3140 Waialae Avenue, Honolulu, HI, 96816, USA
  
• 刊物主题：Pharmacology/Toxicology; Pharmacy; Human Physiology; Pharmaceutical Sciences/Technology; Medical Biochemistry;
• 出版者：Springer Paris
• ISSN：2107-0180

文摘

Placental UDP-glucuronosyltransferase (UGT) enzymes have critical roles in hormone, nutrient, chemical balance and fetal exposure during pregnancy. Placental UGT1A isoforms were profiled and differences between preeclamptic (PE) and non-PE placental UGT expression determined. In third trimester villous placenta, UGT1A1, 1A4, 1A6 and 1A9 were expressed and active in all specimens (n = 10), but UGT1A3, 1A5, 1A7, 1A8 and 1A10 were absent. The UGT1A activities were comparable to human liver microsomes per milligram, but placental microsome yields were only 2 % of liver (1 mg/g of tissue vs. 45 mg/g of tissue). For successful PCR, placental collection and processing within 60 min from delivery, including DNAse and ?00 ng of RNA in reverse transcription were essential and snap freezing in liquid nitrogen immediately was the best preservation method. Although UGT1A6 mRNA was lower in PE (P < 0.001), there were no other significant effects on UGT mRNA, protein or activities. A more comprehensive tissue sample set is required for confirmation of PE interactions with UGT. Placental UGT1A enzyme expression patterns are similar to the liver and a detoxicative role for placental UGT1A is inferred. Keywords Developmental pharmacology Glucuronidation Obstetrics Phase II metabolism