Role of H(2)O(2) in the oxidative effects of zinc exposure in human airway epithelial cells()

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. H(2)O(2) 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 H(2)O(2) production. To determine the role of Zn(2+)-induced H(2)O(2) production in the human airway epithelial cell response to Zn(2+) exposure. BEAS-2B cells expressing the redox-sensitive fluorogenic sensors HyPer (H(2)O(2)) or roGFP2 (E(GSH)) in the cytosol or mitochondria were exposed to 50 µM Zn(2+) for 5 min in the presence of 1 µM of the zinc ionophore pyrithione. Intracellular H(2)O(2) levels were modulated using catalase expression either targeted to the cytosol or ectopically to the mitochondria. HO-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 H(2)O(2). Compartment-directed catalase expression blunted Zn(2+)-induced elevations in cytosolic E(GSH) and the increased expression of HO-1 mRNA levels. Zn(2+) leads to multiple oxidative effects that are exerted through H(2)O(2)-dependent and independent mechanisms.