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Inhibition of endothelial nitric oxide synthase activity and suppression of endothelium-dependent vasorelaxation by 1,2-naphthoquinone, a component of diesel exhaust particles

  • Organ Toxicity and Mechanisms
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An Erratum to this article was published on 05 July 2006

Abstract

Diesel exhaust particles contain redox-active quinones, such as 9,10-phenanthraquinone (9,10-PQ) and 1,2-naphthoquinone (1,2-NQ), which act as potent electron acceptors, thereby altering electron transfer on proteins. We have previously found that 9,10-PQ inhibits constitutive nitric oxide synthase (NOS) activity, by shunting electrons away from NADPH on the cytochrome P450 reductase domain of NOS, and thus suppresses acetylcholine (Ach)-induced vasorelaxation in the aortic ring. However, the effect of 1,2-NQ on endothelial NOS (eNOS) activity is still poorly understood. With the membrane fraction of cultured bovine aortic endothelial cells, we found that 1,2-NQ was a potent inhibitor of eNOS with an IC50 value of 1.4 μM, whereas trans-1,2-dihydroxy-1,2-dihydronaphthalene (1,2-DDN), a redox-negative naphthalene analog of 1,2-NQ, did not show such an inhibitory action. Although 1,2-DDN (5 μM) did not affect Ach-mediated vasorelaxation, 1,2-NQ caused a significant suppression of Ach-induced endothelium-dependent vasorelaxation in the aortic ring. However, 1,2-NQ did not affect sodium nitroprusside-induced endothelium-independent vasorelaxation. These results suggest that 1,2-NQ is an environmental quinone that inhibits eNOS activity, thereby disrupting NO-dependent vascular tone.

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Abbreviations

1,2-NQ:

1,2-Naphthoquinone

1,2-DDN:

trans-1,2-Dihydroxy-1,2-dihydronaphthalene

NO:

Nitric oxide

eNOS:

Endothelial nitric oxide synthase

Ach:

Acetylcholine

SNP:

Sodium nitroprusside

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Acknowledgments

We are especially grateful to Ms. F. Miyamasu for grammatical corrections in the preparation of this manuscript. This research was supported in part by Grant-in-Aid #15390184 and #15659141 (YK) for scientific research from the Ministry of Education, Science, Culture and Sports of Japan.

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Authors and Affiliations

  1. Department of Environmental Medicine, Doctoral Programs in Medical Sciences, Graduate School of Comprehensive Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Yang Sun, Keiko Taguchi, Daigo Sumi & Yoshito Kumagai

  2. Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan

    Shigeru Yamano

  3. Southern California Particle Center and Supersite, Los Angeles, CA, 90095-1772, USA

    Yoshito Kumagai

Authors
  1. Yang Sun
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  2. Keiko Taguchi
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  3. Daigo Sumi
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  4. Shigeru Yamano
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  5. Yoshito Kumagai
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Corresponding author

Correspondence to Yoshito Kumagai.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00204-006-0127-8

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Sun, Y., Taguchi, K., Sumi, D. et al. Inhibition of endothelial nitric oxide synthase activity and suppression of endothelium-dependent vasorelaxation by 1,2-naphthoquinone, a component of diesel exhaust particles. Arch Toxicol 80, 280–285 (2006). https://doi.org/10.1007/s00204-005-0043-3

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  • DOI: https://doi.org/10.1007/s00204-005-0043-3

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