Endogenous S-nitrosoglutathione modifies 5-lipoxygenase expression in airway epithelial cells. Academic Article uri icon

Overview

abstract

  • S-Nitrosoglutathione (GSNO) is an endogenous bronchodilator with several beneficial pulmonary effects. Levels are decreased in the asthmatic airway, and GSNO inhalation has been proposed as an asthma therapy. 5-lipoxygenase (5-LO) is the rate-limiting enzyme in the synthetic pathway for cysteinyl leukotrienes (CysLTs), bronchoconstricting agents that are overproduced in asthma. Here, we have studied the effect of GSNO on the expression of 5-LO in human airway A549 cell lines and in primary normal human tracheobronchial epithelial (NHBE) cells in vitro. GSNO at concentrations of 0.5-1 microM caused a 3- to 6-fold increase in 5-LO expression. However, GSNO at>5 microM significantly inhibited both 5-LO expression and LT production. We also found that airway epithelial cells had gamma-glutamyl transpeptidase (gamma-GT) activity. The effect of 1 microM GSNO on 5-LO expression was prevented by the gamma-GT inhibitor, acivicin, suggesting a convergence of GSNO and CysLT metabolic pathway that may be relevant to asthma. Our data demonstrate that GSNO levels5microM suppresses 5-LO expression. These data suggest that GSNO might inhibit 5-LO expression in the clinical setting.

publication date

  • January 13, 2006

Research

keywords

  • Arachidonate 5-Lipoxygenase
  • Respiratory Mucosa
  • S-Nitrosoglutathione

Identity

PubMed Central ID

  • PMC2644202

Scopus Document Identifier

  • 33645658588

Digital Object Identifier (DOI)

  • 10.1165/rcmb.2005-0336RC

PubMed ID

  • 16415251

Additional Document Info

volume

  • 34

issue

  • 4