NDLI: 9,10-Phenanthrenequinone promotes secretion of pulmonary aldo-keto reductases with surfactant

Content Provider	Springer Nature Link
Author	Matsunaga, Toshiyuki Haga, Mariko Watanabe, Gou Shida, Yuhki Endo, Satoshi Kajiwara, Yu Tanaka, Hiroyuki Inagaki, Naoki El Kabbani, Ossama Hara, Akira
Copyright Year	2012
Abstract	9,10-Phenanthrenequinone (9,10-PQ), a major quinone in diesel exhaust particles, induces apoptosis via the generation of reactive oxygen species (ROS) because of 9,10-PQ redox cycling. We have found that intratracheal infusion of 9,10-PQ facilitates the secretion of surfactant into rat alveolus. In the cultured rat lung, treatment with 9,10-PQ results in an increase in a lower-density surfactant by ROS generation through redox cycling of the quinone. The surfactant contains aldo-keto reductase (AKR) 1C15, which reduces 9,10-PQ and the enzyme level in the surfactant increases on treatment with 9,10-PQ suggesting an involvement of AKR1C15 in the redox cycling of the quinone. In six human cell types (A549, MKN45, Caco2, Hela, Molt4 and U937) only type II epithelial A549 cells secrete three human AKR1C subfamily members (AKR1C1, AKR1C2 and AKR1C3) with the surfactant into the medium; this secretion is highly increased by 9,10-PQ treatment. Using in vitro enzyme inhibition analysis, we have identified AKR1C3 as the most abundantly secreted AKR1C member. The AKR1C enzymes in the medium efficiently reduce 9,10-PQ and initiate its redox cycling accompanied by ROS production. The exposure of A549 cells to 9,10-PQ provokes viability loss, which is significantly protected by the addition of the AKR1C3 inhibitor and antioxidant enzyme and by the removal of the surfactants from the culture medium. Thus, the AKR1C enzymes secreted in pulmonary surfactants probably participate in the toxic mechanism triggered by 9,10-PQ.
Starting Page	407
Ending Page	417
Page Count	11
File Format	PDF
ISSN	0302766X
Journal	Cell and Tissue Research
Volume Number	347
Issue Number	2
e-ISSN	14320878
Language	English
Publisher	Springer-Verlag
Publisher Date	2012-01-27
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	9,10-Phenanthrenequinone Aldo-keto reductase Surfactant Epithelial cell Oxidative stress Human Genetics Proteomics Molecular Medicine
Content Type	Text
Resource Type	Article
Subject	Cell Biology Histology Pathology and Forensic Medicine

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