Superoxide dismutase-like activity of metal substituted lactoferrin derivatives. 1998

R Ishisaka, and T Kanno, and H Kanematsu, and T Utsumi, and J Akiyama, and A A Horton, and T Yoshioka
Institute of Medical Science, Kurashiki Medical Center, Japan.

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.

UI MeSH Term Description Entries
D007501 Iron A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN. Iron-56,Iron 56
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007781 Lactoferrin An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion. Lactotransferrin
D008345 Manganese A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)
D008670 Metals Electropositive chemical elements characterized by ductility, malleability, luster, and conductance of heat and electricity. They can replace the hydrogen of an acid and form bases with hydroxyl radicals. (Grant & Hackh's Chemical Dictionary, 5th ed) Metal
D009504 Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002384 Catalysis The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction. Catalyses
D002413 Cations, Divalent Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis. Divalent Cations
D002417 Cattle Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor. Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003300 Copper A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55. Copper-63,Copper 63

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