TY - JOUR
T1 - An approach to evaluate two-electron reduction of 9,10-phenanthraquinone and redox activity of the hydroquinone associated with oxidative stress
AU - Taguchi, Keiko
AU - Fujii, Sayako
AU - Yamano, Shigeru
AU - Cho, Arthur K.
AU - Kamisuki, Shinji
AU - Nakai, Yumi
AU - Sugawara, Fumio
AU - Froines, John R.
AU - Kumagai, Yoshito
N1 - Funding Information:
We thank Dr. John D. Hayes of the Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, UK, for providing antibody against AKR7A2 isozyme; Dr. Nobuyuki Koga of the Faculty of Nutritional Sciences, Nakamura Gakuen University, Japan, for donation of antibody against NQO1; and Dr. Nobuhiro Shimojo of the Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba, Japan, for his encouragement, and M.S. Rie Koizumi and M.S. Yuya Nishihara of the Master’s Program in Environmental Sciences, University of Tsukuba, for their excellent contribution to this study. We are especially grateful to Ms. F. Miyamasu for grammatical correction in the preparation of the manuscript. This research was supported in part by a Grant-in-Aid Nos. 15390184, 18659167, and 18406003 (Y.K.) for scientific research from the Ministry of Education, Science, Culture, and Sports of Japan. K.T. was awarded an Ishidu Shun Memorial Scholarship. Although the research described in this article has been funded in part by the United States Environmental Protection Agency through Grant R827352-01-0 to UCLA, it has not been subjected to the agency’s required peer and policy review and therefore does not necessarily reflect the views of the agency and no official endorsement should be inferred.
PY - 2007/9/1
Y1 - 2007/9/1
N2 - Quinones are widely used as medicines or redox agents. The chemical properties are based on the reactions against an electron donor. 9,10-Phenanthraquinone (PQ), which is a quinone contaminated in airborne particulate matters, forms redox cycling, not Michael addition, with electron donors. Redox cycling of PQ contributes to its toxicity, following generation of reactive oxygen species (ROS). Detoxification of quinones is generally thought to be two-electron reduction forming hydroquinones. However, a hydroquinone of PQ, 9,10-dihydroxyphenanthrene (PQH2), has been never detected itself, because it is quite unstable. In this paper, we succeeded in detecting PQH2 as its stable derivative, 9,10-diacetoxyphenanthrene (DAP). However, higher concentrations of PQ (> 4 μM) form disproportionately with PQH2, producing the 9,10-phenanthraquinone radical (PQ{radical dot}-) which is a one-electron reducing product of PQ. In cellular experiments using DAP as a precursor of PQH2, it was shown that PQH2 plays a critical role in the oxidative protein damage and cellular toxicity of PQ, showing that two-electron reduction of PQ can also initiate redox cycling to cause oxidative stress-dependent cytotoxicity.
AB - Quinones are widely used as medicines or redox agents. The chemical properties are based on the reactions against an electron donor. 9,10-Phenanthraquinone (PQ), which is a quinone contaminated in airborne particulate matters, forms redox cycling, not Michael addition, with electron donors. Redox cycling of PQ contributes to its toxicity, following generation of reactive oxygen species (ROS). Detoxification of quinones is generally thought to be two-electron reduction forming hydroquinones. However, a hydroquinone of PQ, 9,10-dihydroxyphenanthrene (PQH2), has been never detected itself, because it is quite unstable. In this paper, we succeeded in detecting PQH2 as its stable derivative, 9,10-diacetoxyphenanthrene (DAP). However, higher concentrations of PQ (> 4 μM) form disproportionately with PQH2, producing the 9,10-phenanthraquinone radical (PQ{radical dot}-) which is a one-electron reducing product of PQ. In cellular experiments using DAP as a precursor of PQH2, it was shown that PQH2 plays a critical role in the oxidative protein damage and cellular toxicity of PQ, showing that two-electron reduction of PQ can also initiate redox cycling to cause oxidative stress-dependent cytotoxicity.
KW - 9,10-Phenanthraquinone
KW - Disproportionation
KW - Redox cycling
KW - Two-electron reduction
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U2 - 10.1016/j.freeradbiomed.2007.05.021
DO - 10.1016/j.freeradbiomed.2007.05.021
M3 - Article
C2 - 17664142
AN - SCOPUS:34547093431
VL - 43
SP - 789
EP - 799
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
IS - 5
ER -