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Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia

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Abstract

Exposure of cultured pulmonary artery endothelial cells to 95% O2 resulted in the following sequence of events: decrease in [3H]thymidine incorporation after 24 h; increase of intracellular glutathione (GSH) and loss of cellular protein after 48 h; increase of spontaneous and decrease of provoked prostacyclin formation as well as increased release of cellular LDH after 72 h. This oxygen toxicity model was used to study the following 2 questions. (1) What is the relative importance of the GSH redox cycle compared to catalase as antioxidative defense against hyperoxia? Endothelial cells were grown in selenium-depleted medium to inhibit glutathione peroxidase activity. Endothelial GSH biosynthesis was inhibited by buthionine sulfoximine. Catalase activity was reduced by aminotriazole. Endothelial cells with an impaired GSH redox cycle were easily killed by hyperoxia within 24 h, while inhibition of catalase did not enhance the susceptibility of endothelial cells to hyperoxia. (2) Can endothelial GSH content be increased by exogenous sulfhydryl reagents and does this results in an increase of endothelial cells’ resistance to hyperoxia? Exogenous GSH, N-acetylcysteine, cysteine, and L-2-oxothiazolidine-4-carboxylate (L-2-oxo) increased intracellular GSH. All sulfhydryl reagents (with the exception of L-2-oxo) protected endothelial cells from hyperoxia. Concentrations of exogenous GSH and N-acetylcysteine that did not increase intracellular GSH reduced hyperoxia-induced endothelial cell injury. Thus the capacity of the GSH redox cycle rather than intracellular GSH levels or catalase determines endothelial cells’ resistance to hyperoxia.

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  1. Division of Clinical Pathophysiology and Experimental Medicine/Department of Internal Medicine, Justus Liebig University of Giessen, FRG

    Norbert Suttorp, Simon Kästle & Heinz Neuhof

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  1. Norbert Suttorp
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  2. Simon Kästle
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  3. Heinz Neuhof
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Suttorp, N., Kästle, S. & Neuhof, H. Glutathione redox cycle is an important defense system of endothelial cells against chronic hyperoxia. Lung 169, 203–214 (1991). https://doi.org/10.1007/BF02714155

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