Superoxide dismutase-like activity of metal substituted lactoferrin derivatives.
Lactoferrin (LF) is an iron-binding glycoprotein present in various secretions including milk and the specific granules of neutrophils. The main biological properties of this protein are thought to concern the regulation of iron absorption, antimicrobial activity and modulation of neutrophil activity. Copper bound LF (Cu-LF) inhibited the stimulation-dependent reduction of cytochrome c (Cyt. c) in guinea pig peritoneal neutrophils (GPMN) but were without effect on NADPH oxidase activity of the respiratory burst. However, Cu-LF stimulated the stimulation-dependent production of hydrogen peroxide as seen with superoxide dismutase (SOD). Similar but weaker inhibition of Cyt. c reduction than that shown by Cu-LF was observed with manganese-LF (Mn-LF) but not with ferrous-LF (Fe-LF) or apo-LF (Apo-LF). The inhibitory activity was concentration-dependent and the ID50s of Cu-LF and of Mn-LF were 0.1 and 5 microM, respectively. Reactive oxygen species (ROS) detected by luminol chemiluminescence (LCL) of stimulated-GPMN were partially inhibited by Cu-LF. Changes in LCL of stimulated GPMN induced by Cu-LF were similar to those of superoxide dismutase (SOD). Thus, it is concluded that low concentrations of Cu-LF had SOD-like activity and high concentrations of Cu-LF inhibited the stimulation-dependent generation of ROS.
Ishisaka
R
R
Institute of Medical Science, Kurashiki Medical Center, Japan.
Kanno
T
T
Kanematsu
H
H
Utsumi
T
T
Akiyama
J
J
Horton
A A
AA
Yoshioka
T
T
D000818:Animals; D001059:Apoproteins / Q000378:metabolism; D002384:Catalysis; D002413:Cations, Divalent / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D006168:Guinea Pigs; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D007781:Lactoferrin / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism / Q000494:pharmacology; D008670:Metals / Q000378:metabolism* / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology; D016897:Respiratory Burst; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism
D001059:Apoproteins; D002413:Cations, Divalent; D003574:Cytochrome c Group; D008670:Metals; D013481:Superoxides; D008345:Manganese; D003300:Copper; D007501:Iron; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D007781:Lactoferrin