title: Auranofin modulates human neutrophil superoxide production and protein phosphorylation.
abstract: The effect of auranofin (AF) was examined on human neutrophil superoxide production and protein phosphorylation stimulated by phorbol esters. Low concentrations of auranofin (less than or equal to 0.5 microM) enhanced while higher concentrations (0.5-10 microM) inhibited superoxide release stimulated by a suboptimal concentration (0.005 microM) of phorbol myristate acetate (PMA). The enhancing but not the inhibitory effect of AF was lost if a maximal stimulating dose (0.05 microM) of PMA was used. In contrast AF had a biphasic effect on protein phosphorylation regardless of the stimulating concentration of PMA. Comparison of the dose-response curves for these effects of AF suggest that although changes in protein phosphorylation may be partly responsible for altered activity of the NADPH oxidase responsible for superoxide production, it is unlikely that they are mediated by a direct effect of AF on protein kinase C. Also, measurement of 3H-PDBu-binding to neutrophils showed that these actions of AF could not be attributed to altered binding of phorbol esters to their cellular receptor (protein kinase C).
authors.affiliation: Rheumatology Unit, University of Adelaide, Queen Elizabeth Hospital, Woodville, South Australia.
authors.forename: N P
authors.initials: NP
authors.lastname: Hurst
authors.forename: L
authors.initials: L
authors.lastname: Gorjatschko
authors.forename: W H
authors.initials: WH
authors.lastname: Betts
authors.forename: P D
authors.initials: PD
authors.lastname: Zalewski
authors.forename: I J
authors.initials: IJ
authors.lastname: Forbes
mesh_terms: D001310:Auranofin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013481:Superoxides / Q000096:biosynthesis* / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism
chemical_list: D013481:Superoxides; D001310:Auranofin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate