Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme

Nobumitsu Hanioka, Yuri Takeda, Toshiko Tanaka-Kagawa, Keiko Hayashi, Hideto Jinno, Shizuo Narimatsu

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The effects of bisphenol A (BPA) on UDP-glucuronosyltransferase 1A6 (UGT1A6) activities in microsomes from human livers and yeast cells expressing human UGT1A6 (humUGT1A6) were investigated. Serotonin (5-HT) and 4-methylumbelliferone (4-MU) were used as the substrates for UGT1A6. BPA dose-dependently inhibited 5-HT and 4-MU glucuronidation activities in both enzyme sources. The IC50 values of BPA for 5-HT and 4-MU glucuronidation activities were 156 and 163 μM for liver microsomes, and 84.6 and 80.3 μM for yeast cell microsomes expressing humUGT1A6, respectively. The inhibitory pattern of BPA for 5-HT and 4-MU glucuronidation activities in human liver microsomes exhibited a mixture of competitive and noncompetitive components, with Ki values of 84.9 and 72.3 μM, respectively. In yeast cell microsomes expressing humUGT1A6, 5-HT glucuronidation activities were noncompetitively inhibited by BPA (Ki value, 65.5 μM), whereas the inhibition of 4-MU glucuronidation activities by BPA exhibited the mixed type (Ki value, 42.5 μM). These results suggest that BPA interacts with human UGT1A6 enzyme, and that the interaction may contribute to the toxicity, such as hormone disruption and reproductive effects, of BPA.

Original languageEnglish
Pages (from-to)407-412
Number of pages6
JournalEnvironmental Toxicology
Volume23
Issue number3
DOIs
Publication statusPublished - May 26 2008

Keywords

  • 4-methylumbelliferone
  • Bisphenol A
  • Interaction
  • Serotonin
  • UGT1A6

ASJC Scopus subject areas

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Hanioka, N., Takeda, Y., Tanaka-Kagawa, T., Hayashi, K., Jinno, H., & Narimatsu, S. (2008). Interaction of bisphenol A with human UDP-glucuronosyltransferase 1A6 enzyme. Environmental Toxicology, 23(3), 407-412. https://doi.org/10.1002/tox.20345