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Differential Roles of Hydrogen Peroxide in Adaptive and Inflammatory Gene Expression Induced by Exposure of Human Airway Epithelial Cells to Zn2+
Silbajoris, R., A. Henriquez, P. Wages, AND J. Samet. Differential Roles of Hydrogen Peroxide in Adaptive and Inflammatory Gene Expression Induced by Exposure of Human Airway Epithelial Cells to Zn2+. Presented at American Thoracic Society, May 18 - 22, 2013.
This is an abstract of scientific work to be presnted at the ATS meeting May 18-22, 2013
Oxidant stress is believed to play an important role in particulate matter (PM)–mediated toxicity in the respiratory tract. Zinc (Zn2+) is a ubiquitous component of PM that has been shown to induce adverse responses such as inflammatory and adaptive gene expression in airway epithelial cells. We have previously shown that Zn2+ exposure disregulates signaling through a mechanism involving the inhibition of protein tyrosine phosphatase activity, and reported an increase in mitochondrially-derived H2O2 in the cytosol of cells exposed to Zn2+. Since H2O2 is involved in the redox regulation of phosphatases under physiological conditions, we investigated the contributing role of H2O2 in Zn2+-induced alterations in gene expression. We specifically investigated the role of H2O2 in Zn2+-induced expression of the adaptive, oxidant responsive gene heme oxygenase-1 (HO-1) and the inflammatory mediators COX-2 and IL-8 in BEAS 2B human bronchial epithelial cells. Exposure of BEAS 2B cells to 10-100 µM zinc sulfate for 2 h induced mRNA transcript levels for IL-8, COX-2 and HO-1 in a dose-dependent manner, as measured by RT-PCR. mRNA expression of IL-8 and COX-2 increased 8-fold compared to a media control at the highest dose of Zn2+, while HO-1 mRNA increased 37-fold. Adenoviral overexpression of catalase (AdCat) blunted Zn2+-induced expression of HO-1. In contrast, the expression of COX-2 and IL-8 was not different between catalase-overexpressing cells and BEAS 2B cells transduced with a control (Ad-CMV) vector. These results show that exposure to Zn2+ induces changes in gene expression through the activation of H2O2-dependent and independent mechanisms, indicating that Zn2+-mediated toxicity occurs through the disregulation of multiple regulatory pathways simultaneously. These findings further suggest that the non-redox active transition metal Zn2+ can induce oxidative effects both through direct interactions with regulatory thiols as well as through the generation of reactive oxygen species of cellular origin. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.