TRANSGENE TARGETING OF ANTIOXIDANTS AND LUNG INJURY

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DESCRIPTION: (From the authors' abstract) Despite supportive evidence for oxidative stress occurring in the lung following particle exposures, there is little known about the source of the reactive oxygen species, the cellular or extracellular compartment they are produced in, the compartment in which they react and cause their deleterious effects, as well as the cellular or extracellular target(s) which are modified. The investigators hypothesize that inhaled environmental agents, which exert their toxic effects on the lung, via reactive oxygen species, do so in a highly compartmentalized fashion. Depending on the compartment where increased oxidative stress is being subjected, certain lung cell-types may be more vulnerable to depleting their compartmentalized antioxidant reserves, thus proving them to be at increased risk for injury. This application will test this hypothesis by systematically overexpressing antioxidant enzymes in a highly compartmentalized lung-specific fashion and studying their contribution to preserving lung function following inhalational exposure to environmental particles (residual oil fly ash, silica concentrated ambient dust, Mt. St. Helen's volcanic ash), and will target the overexpression of CuZn-SOD, Mn-SOD, EC-SOD, catalase, and glutathione peroxidase to the mouse lung using the surfactant protein C promoter. Insights gained from these studies could be used for formulating novel therapies for the prevention and/or treatment of particle-induced lung disease.