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Biochem J. 2000 Jul 15;349(Pt 2):455-61.

Glutathione peroxidase-1 but not -4 is involved in the regulation of cellular 5-lipoxygenase activity in monocytic cells.

Author information

1
Institute of Pharmaceutical Chemistry, University of Frankfurt, Marie-Curie-Str. 9, D-60439 Frankfurt, Germany.

Abstract

In contrast to neutrophils or B-lymphocytes, cells of the monocytic lineage like rat macrophages, human peripheral blood monocytes and Mono Mac 6 cells contain a strong inhibitor of 5-lipoxygenase (5-LO) activity, which scavenges hydroperoxides and inhibits 5-LO activity in broken-cell preparations in the absence of exogenously added thiols. Chromatographic purification of the inhibitor from the human monocytic cell line Mono Mac 6 and amino acid sequence analysis revealed that the inhibitory factor is glutathione peroxidase-1 (GPx-1). In contrast to the peroxidase activity of GPx-1, 5-LO inhibition by GPx-1 was supported by beta-mercaptoethanol and there was no absolute requirement for millimolar concentrations of glutathione or dithiothreitol. These cofactor characteristics suggest that both activities address distinct catalytic properties of GPx-1. 5-LO inhibition by GPx-1 was not due to direct GPx-5-LO protein-protein interactions, since GPx-1 did not bind to immobilized 5-LO. Interestingly, 5-LO derived from granulocytes was significantly more resistant against GPx-1 inhibition than B-lymphocytic 5-LO, which correlates with the respective cellular 5-LO activities. In summary, the data suggest that, in addition to previously reported phospholipid hydroperoxide glutathione peroxidase (GPx-4), GPx-1 is an efficient inhibitor of 5-LO even at low thiol concentrations, and is involved in the regulation of cellular 5-LO activity in various cell types.

PMID:
10880344
PMCID:
PMC1221168
DOI:
10.1042/0264-6021:3490455
[Indexed for MEDLINE]
Free PMC Article

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