Abstract
Peroxiredoxin 6 (Prdx6), a recently described enzyme with glutathione peroxidase (GPX) activity, plays an important role in lung anti‐oxidant defense. Since Prdx6, unlike GPX1, can reduce phospholipid hydroperoxides, we compared the effects of knock‐out of the two enzymes on the response of mice to hyperoxia. The time (h) to 50% lethality (LT50) on exposure to 85% O2 was 148±12 for wild type (C57 Bl/6), 123±10 for GPx1‐/‐, and 98.5±8.6 for Prdx6‐/‐. After 100% O2 exposure for 60 h, protein content and nucleated cells in the bronchoalveolar lavage fluid and lung wet/dry increased significantly in wild type lungs; changes with GPx1 ‐/‐ lungs were similar to wild type, but Prdx6‐/‐ lungs showed markedly increased injury. Lung thiobarbituric acid reactive substances (TBARS) were 114 ± 8.5 in wild type, 148 ±16.3 in Gpx1‐/‐, and 256 ±17.2 in Prdx6‐/‐ (pmol/mg). Exposure of isolated mouse pulmonary microvascular endothelial cells to 50 μM t‐butyl hydroperoxide (t‐BOOH) for 2 hrs resulted in 34 % cell death for wild type, 65.2% for GPX1‐/‐, and 96.6% for Prdx6‐/‐. Thus, Prdx6 null mice are significantly more sensitive to hyperoxic stress than the GPX1 null indicating that repair of lipid peroxidation (i.e. membrane damage) plays a major role in antioxidant defense.
Published Version
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