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Original Article

Role of Selenium-Dependent Glutathione Peroxidase in Antioxidant Defenses in Rat Alveolar Macrophages

, , &
Pages 921-936 | Published online: 02 Jul 2009
 

Abstract

Glutathione peroxidase is a crucial component of cellular antioxidant defenses. Using tertiary butyl hydroperoxide (tBOOH) as a model for oxidant stress in alveolar macrophages, we determined the effectiveness of glutathione peroxidase in preventing both cell “death” (lactate dehydrogenase release) and more subtle alterations in cell function. The KM of glutathione peroxidase for tBOOH was 54 μM, and the Vmax was 26 nmol/min/106 cells in alveolar macrophages. Concentrations of tBOOH greater than 100 μM caused lactate dehydrogenase release; however, a lag greater than 30 min was observed when with 10 μM tBOOH. With 200 μM tBOOH, the rate of decrease in membrane potential, measured by 3,3′ -dipentyloxacarbocyanine iodide fluorescence, inversely correlated with glutathione peroxidase. Computer-enhanced microscopy showed that this fluorescence predominately was in mitochondria. NADPH fluorescence was altered in selenium-deficient alveolar macrophages; the tBOOH-dependent rate of NADPH oxidation was slowed, and higher concentrations of tBOOH were required to disturb the steady state NADPH/NADP+ ratio. Although alteration in NADPH or glutathione oxidation can reflect oxidant stress and can adversely affect cell function, such a change does not dictate irreversible injury. Nevertheless, irreversible injury by oxidants appears to involve an overwhelming of the glutathione-NADPH antioxidant system.

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