Abstract
Air pollution is a global public health concern linked to cardiopulmonary morbidity and mortality. Quinones are components of ambient particulate matter (PM) air pollution and may contribute to health effects through oxidative mechanisms. 1,2-naphthoquinone (1,2-NQ) is an electrophile that can adduct macromolecules and participate in single electron redox reactions to produce reactive oxygen species. We have previously shown that exposure to 1,2-NQ increases mitochondrial H2O2 production, leading to activation of inflammatory signaling. In the present study, we utilized extracellular flux analyses to characterize 1,2-NQ-induced disruption of mitochondrial function in human airway epithelial cells. 1,2-NQ caused a marked increase in the oxygen consumption rate (OCR) that was shown to be largely attributable to redox cycling in the cytosol using permeabilized-cell and isolated mitochondria preparations. In these preparations, 1,2-NQ impaired Complex I-linked substrate utilization, specifically the oxidation of pyruvate but not glutamate. Complex I activity of NADH oxidation was not blunted by 1,2-NQ exposure, suggesting inhibition of pyruvate-specific uptake and/or metabolism. In addition, 1,2-NQ exposure did not affect Complex II-linked substrate oxidation. These findings show that exposure to redox-active compounds like 1,2-NQ can elicit H2O2 production through redox cycling and mitochondrial dysfunction simultaneously. Accurate interpretation of OCR effects by xenobiotic exposures requires consideration of alternative sources of oxygen consumption. this Abstract of a proposed presentation does not necessarily reflect EPA policy.
Published Version
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