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

Yang Sun, Keiko Taguchi, Daigo Sumi, Shigeru Yamano, Yoshito Kumagai

Research output: Contribution to journalArticle

32 Citations (Scopus)

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 tgljoint @ Set Line Joint Styleon 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.

Original languageEnglish
Pages (from-to)280-285
Number of pages6
JournalArchives of Toxicology
Volume80
Issue number5
DOIs
Publication statusPublished - 2006 May
Externally publishedYes

Keywords

  • 1,2-Naphthoquinone
  • Diesel exhaust particles
  • Endothelial nitric oxide synthase
  • Nitric oxide
  • Vasorelaxation

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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