Inhibition by superoxide dismutase-mimetic copper complexes of phorbol ester-induced respiratory burst in human granulocytes.
Two superoxide dismutase-mimetic lipophilic copper complexes, Cu(II)2(indomethacin)4 [Cu(II)2(indo)4] and Cu(II)2(3,5-diisopropylsalicylate)4 [Cu(II)2(3,5-DIPS)4], were tested for their effects on the respiratory burst of intact human granulocytes and on xanthine oxidase, under conditions where superoxide and hydrogen peroxide were generated. The effect of the copper complexes on these enzyme systems (as opposed to their dismutase effect on superoxide) was determined by measuring oxygen uptake with an oxygen meter. It was found that, after a short delay, both systems were inhibited markedly by micromolar amounts of these complexes. This inhibition was prevented by treatment with EDTA or catalase if added prior to starting the reaction. Similar inhibitory effects were seen using copper sulfate. It appears that these lipophilic SOD-mimetic compounds can, in the presence of H2O2 and O2-, give rise to a species that can inhibit some component of the respiratory burst oxidase or protein kinase C in intact granulocytes and xanthine oxidase in solution. The observed decrease in O2- levels observed upon addition of these compounds is likely due to inhibition of the source and not to their SOD-mimetic properties.
Pelletier
O
O
Department of Experimental Oncology, Ottawa Regional Cancer Centre, Canada.
Hill
I
I
Birnboim
H C
HC
D003300:Copper / Q000494:pharmacology*; D019327:Copper Sulfate; D006098:Granulocytes / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology*; D009942:Organometallic Compounds / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D016897:Respiratory Burst / Q000187:drug effects*; D012459:Salicylates / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013997:Time Factors; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D009942:Organometallic Compounds; D010703:Phorbol Esters; D012459:Salicylates; C067228:copper tetrakis(3,5-diisopropylsalicylic acid); C063001:cupric(indomethacinate)4complex; D003300:Copper; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D019327:Copper Sulfate; D010100:Oxygen; D007213:Indomethacin