Phenanthraquinone affects endothelial nitric oxide synthase activity through modification of the thiol group: An alternative inhibition mechanism

Keiko Taguchi, Yoshito Kumagai, Akiko Endo, Makoto Kikushima, Yuji Ishii, Nobuhiro Shimojo

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)571-574
Number of pages4
JournalJournal of Health Science
Volume47
Issue number6
DOIs
Publication statusPublished - 2001

Keywords

  • Diesel exhaust particle
  • Nitric oxide synthase
  • Phenanthraquinone
  • Thiol

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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