Glucocerebroside inhibits NADPH oxidase activation in cell-free system

We reported earlier that monocytes and macrophages from patients with type I Gaucher disease have a decreased capacity to generate superoxide anion (O2−) on stimulation with opsonized S. aureus or formyl-methionyl-leucyl-phenylalanine. In this study, various forms of the cell-free assay system were...

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Veröffentlicht in:Biochimica et biophysica acta Jg. 1688; H. 3; S. 197 - 203
Hauptverfasser: Moskwa, Patryk, Palicz, Anita, Paclet, Marie-Hélène, Dagher, Marie-Claire, Erdős, Melinda, Maródi, László, Ligeti, Erzsébet
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Netherlands Elsevier B.V 05.04.2004
Schlagworte:
Cell-Free System
Cloning, Molecular
Enzyme Activation - drug effects
Gaucher disease
Glucocerebroside
Glucosylceramides - pharmacology
Humans
Kinetics
NADPH oxidase
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - blood
NADPH Oxidases - drug effects
Neutrophils - enzymology
Recombinant Proteins - antagonists & inhibitors
Recombinant Proteins - metabolism
Superoxides - blood
Xanthine Oxidase - blood
Glucocerebroside
NADPH oxidase
Gaucher disease
ISSN:0925-4439, 0006-3002, 1879-260X
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Zusammenfassung:We reported earlier that monocytes and macrophages from patients with type I Gaucher disease have a decreased capacity to generate superoxide anion (O2−) on stimulation with opsonized S. aureus or formyl-methionyl-leucyl-phenylalanine. In this study, various forms of the cell-free assay system were used to probe the hypothesis that glucocerebroside (GC) accumulating in Gaucher patients' phagocytes may interfere with the activation of NADPH oxidase. Xanthine/xanthine oxidase assay was applied to explore the possibility that GC may scavenge O2−. We found that addition of GC to the crude, semirecombinant or fully purified cell-free systems inhibited activation of NADPH oxidase in a concentration-dependent manner. The inhibitory effect of GC could be overcome by increased concentrations of p47phox and p67phox. In contrast, O2− generation was not decreased by GC added to the assembled, catalytically active enzyme complex. In the xanthine/xanthine oxidase system, GC had no effect on the generation of O2−. These data indicate that assembly of the respiratory burst oxidase of phagocytic cells may be a possible target of the pathologic actions of GC.
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content type line 23
ISSN:0925-4439
0006-3002
1879-260X
DOI:10.1016/j.bbadis.2003.12.002