Phenanthraquinone Affects Endothelial Nitric Oxide Synthase Activity through Modification of the Thiol Group : An Alternative Inhibition Mechanism
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概要
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Phenanthraquinone(PQ) is a component of diesel exhaust particles which inhibits nitric oxide synthase(NOS) activity by shunting electrons away from the normal catalytic pathway of the enzyme and which can oxidize proximal protein sulfhydryls. In the present study, we examined the possibility that PQ may also modify critical thiol residues on endothelial NOS (eNOS), leading to a disruption of catalytic activity. PQ and the thiol-modifying agent N-ethylmaleimide (NEM) suppressed NO formation from L-arginine by the total membrane fraction of bovine aortic endothelial cells in a concentration-dependent manner. The dithiol agent dithiothreitol(DTT) completely blocked NEM-mediated inhibition of eNOS activity. In contrast, PQ-inhibited eNOS activity was reduced by DTT, but not by the monothiol agent glutathione. These results suggest that PQ-mediated suppression of eNOS activity involves not only uncoupling of the electron transport of this enzyme, but also modification of presumably the proximal protein sulfhydryls that play an important role in the maximal catalytic activity.
- 公益社団法人日本薬学会の論文
- 2001-12-01
著者
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Taguchi Keiko
Dep. Of Medical Biochemistry Tohoku Univ. Graduate School Of Medicine
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Taguchi Keiko
Master's Program In Enbironmental Sciences
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KUMAGAI Yoshito
Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba
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SHIMOJO Nobuhiro
Department of Environmental Medicine, Institute of Community Medicine, University of Tsukuba
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Ishii Yuji
Department Of Environmental Medicine Institute Of Community Medicine
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Endo Akiko
Master's Program in Enbironmental Sciences
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Kikushima Makoto
Doctoral Program in Medical Sciences, University of Tsukuba
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Endo Akiko
Master's Program In Enbironmental Sciences
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Kumagai Yoshito
Department Of Environmental Medicine Institute Of Community Medicine
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Shimojo Nobuhiro
Department Of Environmental Medicine Institute Of Community Medicine
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Kikushima Makoto
Doctoral Program In Medical Sciences University Of Tsukuba
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