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Role of H2O2 in the Oxidative Effects of Zinc Exposure in Human Airway Epithelial Cells
Citation:
Wages, P., R. Silbajoris, A. Speen, L. Brighton, A. Henriquez, H. Tong, P. Bromberg, Steve Simmons, AND J. Samet. Role of H2O2 in the Oxidative Effects of Zinc Exposure in Human Airway Epithelial Cells. Redox Biology. Elsevier B.V., Amsterdam, Netherlands, 3:47-55, (2014).
Impact/Purpose:
This is a research article on a mechanistic study examining the oxidative properties and effects of the ubiquitous metallic PM component Zn2+ on cultured human airway epithelial cells. This work fits under ACE 242.
Description:
Human exposure to particulate matter (PM) is a global environmental health concern. Zinc (Zn(2+)) is a ubiquitous respiratory toxicant that has been associated with PM health effects. However, the molecular mechanism of Zn(2+) toxicity is not fully understood. H202 and Zn(2+) have been shown to mediate signaling leading to adverse cellular responses in the lung and we have previously demonstrated Zn(2+) to cause cellular H202 production. To determine the role of Zn(2+)-induced H202 production in the human airway epithelial cell response to Zn(2+) exposure. BEAS-28 cells expressing the redox-sensitive fluorogenic sensors HyPer (H202) or roGFP2 (EGSH) in the cytosol or mitochondria were exposed to 50 uM Zn(2+) for 5min in the presence of 1 uM of the zinc ionophore pyrithione. Intracellular H202 levels were modulated using catalase expression either targeted to the cytosolor ectopically to the mitochondria. H0-1 mRNA expression was measured as a downstream marker of response to oxidative stress induced by Zn(2+) exposure. Both cytosolic catalase overexpression and ectopic catalase expression in mitochondria were effective in ablating Zn(2+)-induced elevations in H202. Compartment-directed catalase expression blunted Zn(2+)-induced elevations in cytosolic EGSH and the increased expression of H0-1 mRNA levels. Zn(2+) leads to multiple oxidative effects that are exerted through H202-dependent and independent mechanisms.