Oxidant stress stimulates mucin secretion and PLC in airway epithelium via a nitric oxide-dependent mechanism

The American Journal of Physiology
D T WrightK B Adler

Abstract

Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide variety of respiratory diseases. We investigated mechanisms of ROS-induced mucin secretion by guinea pig tracheal epithelial (GPTE) cells in primary culture, and ROS-induced activation of the second messenger-producing enzyme phospholipase C (PLC), in GPTE cells and in a virally transformed cell line (BEAS-2B) derived from human bronchial epithelium. Mucin secretion was measured by a monoclonal antibody-based enzyme-linked immunosorbent assay, and PLC activation was assessed by anion exchange chromatography. ROS generated enzymatically by xanthine oxidase (XO, 500 microM) in the presence of purine (500 microM) enhanced release of mucin by GPTE cells and activated PLC in GPTE and BEAS cells. Hypersecretion of mucin and activation of PLC in response to purine + XO appeared to occur via an intracellular pathway(s) dependent on endogenously produced nitric oxide and possibly intracellularly generated oxidants. Both responses could be blocked or attenuated by preincubation of the cells with NG-monomethyl-L-arginine, an inhibitor of the enzyme nitric oxide synthase, or with dimethylthiourea, a compound that can react with a variety of intracellular oxida...Continue Reading

Citations

Jan 21, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jason D ConwayC William Davis
Mar 4, 2008·American Journal of Respiratory Cell and Molecular Biology·Joungjoa ParkKenneth B Adler
Nov 26, 2002·American Journal of Respiratory and Critical Care Medicine·Souheil El-ChemalyRosanna Forteza
Oct 7, 2003·American Journal of Physiology. Lung Cellular and Molecular Physiology·Thomas GrayPaul Nettesheim
Sep 12, 2012·Oxidative Medicine and Cellular Longevity·O F Araneda, M Tuesta
Jul 4, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Sidra M HoffmanYvonne M W Janssen-Heininger
Sep 25, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tatsuro NakamuraTakahisa Murata

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