PMID: 2496978Apr 1, 1989Paper

Involvement of glutathione peroxidase activity in the stimulation of 5-lipoxygenase activity by glutathione-depleting agents in human polymorphonuclear leukocytes

European Journal of Biochemistry
A HatzelmannV Ullrich

Abstract

We recently demonstrated activation of 5-lipoxygenase activity in human polymorphonuclear leukocytes (PMN) on preincubation of the cells with glutathione-depleting agents, namely 1-chloro-2,4-dinitrobenzene (Dnp-C1) and azodicarboxylic acid bis[dimethylamide] (diamide). In this paper we show that Dnp-C1, but not diamide, impairs the reduction of added organic peroxides in whole PMN. Also, since co-incubation of fatty acid hydroperoxides with arachidonate caused activation of 5-lipoxygenase, we propose that Dnp-C1 increases the peroxide level in PMN which is required for the onset of lipoxygenase activity. This could be substantiated in PMN homogenates by a glutathione-dependent depression of arachidonate 5-lipoxygenation. At higher arachidonate concentrations and in the presence of Ca2+ the glutathione effect was not observed but additional glutathione peroxidase also blocked this maximally stimulated 5-lipoxygenase. Together with other experiments, it became obvious that the formation of leukotrienes, but also of 15-lipoxygenase products, requires a sharply defined threshold level of fatty acid hydroperoxides which are generated by the lipoxygenases and counteracted by glutathione-dependent peroxidase(s). Dnp-C1 influences thi...Continue Reading

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Citations

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