Reduction of cytotoxic p-Quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B10

Toshiyuki Matsunaga, Satoshi Endo, Mayuko Takemura, Midori Soda, Keiko Yamamura, Kazuo Tajima, Takeshi Miura, Tomoyuki Terada, Ossama El-Kabbani, Akira Hara

研究成果: Article

6 引用 (Scopus)

抜粋

2-tert-Butylhydroquinone (BHQ), an antioxidant used as a food additive, exhibits an anticancer effect, whereas it is carcinogenic in rodents at high doses. BHQ is metabolized into cytotoxic tertbutylquinone (BQ), which is further converted to 6-tert-butyl-2,3-epoxy-4-hydroxy-5-cyclohexen-1-one (TBEH) through 6-tert-butyl-2,3-epoxy-4-benzoquinone (TBE), which induces chromosomal aberration. The reductases for BQ and TBE may be protective against the toxicity of the two p-quinones, but the responsible human enzymes remain unidentified. In this study, we compared the ability of 12 human recombinant enzymes in the aldo-keto reductase (AKR) and short-chain dehydrogenase/reductase superfamilies to reduce BQ and TBE. Among them, AKR1B10 was the most efficient catalyst of the stoichiometric two-electron reduction of BQ and TBE into BHQ and TBEH, respectively. BQ and TBE are more cytotoxic towards endothelial cells than BHQ and TBEH, and their cytotoxicity was decreased by the overexpression of AKR1B10 in the cells. Additionally, AKR1B10 gene expression in human HCT116 cells was up-regulated by treatments with BHQ, BQ and TBE. These results suggest a role for the enzyme in protection at least against the toxicity of the two p-quinone metabolites of BHQ.

元の言語English
ページ(範囲)553-558
ページ数6
ジャーナルDrug Metabolism and Pharmacokinetics
27
発行部数5
DOI
出版物ステータスPublished - 01-01-2012
外部発表Yes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

フィンガープリント Reduction of cytotoxic p-Quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B10' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    Matsunaga, T., Endo, S., Takemura, M., Soda, M., Yamamura, K., Tajima, K., Miura, T., Terada, T., El-Kabbani, O., & Hara, A. (2012). Reduction of cytotoxic p-Quinone metabolites of tert-butylhydroquinone by human aldo-keto reductase (AKR) 1B10. Drug Metabolism and Pharmacokinetics, 27(5), 553-558. https://doi.org/10.2133/dmpk.DMPK-12-NT-012