Aldo-keto reductase 1C15 as a quinone reductase in rat endothelial cell: Its involvement in redox cycling of 9,10-phenanthrenequinone

Toshiyuki Matsunaga, Yuhki Shinoda, Yukari Inoue, Mariko Haga, Satoshi Endo, Ossama El-Kabbani, Akira Hara

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)


9,10-Phenanthrenequinone (9,10-PQ), a redox-active quinone in diesel exhausts, triggers cellular apoptosis via reactive oxygen species (ROS) generation in its redox cycling. This study found that induction of CCAAT/enhancer-binding protein-homologous protein (CHOP), a pro-apoptotic factor derived from endoplasmic reticulum stress, participates in the mechanism of rat endothelial cell damage. The 9,10-PQ-mediated CHOP induction was strengthened by a proteasome inhibitor (MG132) and the MG132-induced cell sensitization to the 9,10-PQ toxicity was abolished by a ROS inhibitor, suggesting that ROS generation and consequent proteasomal dysfunction are responsible for the CHOP up-regulation caused by 9,10-PQ. Aldo-keto reductase (AKR) 1C15 expressed in rat endothelial cells reduced 9,10-PQ into 9,10-dihydroxyphenanthrene concomitantly with superoxide anion formation, implying its participation in evoking the 9,10-PQ-redox cycling. The 9,10-PQ-induced damage was augmented by AKR1C15 over-expression. 9,10-PQ also provoked the AKR1C15 up-regulation, which sensitized against the quinone toxicity. These results suggest the presence of a negative feedback loop exacerbating the quinone toxicity in rat endothelial cells.
Original languageEnglish
Pages (from-to)848 - 857
Number of pages10
JournalFree Radical Research
Issue number7
Publication statusPublished - 2011

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