Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver.
Intravenous injection of bovine or human lactoferrin (6.25 x 10(-2) mumol/100 g body wt) in rats resulted in marked reduction of hepatic iron uptake from transferrin and asialotransferrin. The effect was dose dependent, saturable at approximately 5 mg/100 g body wt, and independent of lactoferrin's iron content. At this dose level, iron uptake from transferrin was reduced by 28% and from asialotransferrin by 43% in experiments lasting 90 min. Bovine lactoperoxidase, another basic protein, was similarly effective. The clearance of asialofetuin and pinocytosis of polyvinylpyrrolidone remained unaffected. Perfusion of isolated rat livers at 4 degrees C showed a strong reduction in asialotransferrin binding in the presence of lactoferrin. Chromatography of hepatic heparan sulfate proteoglycan on immobilized lactoferrin, lactoperoxidase, asialotransferrin, and transferrin showed that it possessed affinity for each of these proteins, more for the first two than the latter two. Heparan sulfate proteoglycan binding and efficacy in reducing hepatic iron uptake were also studied after selective modifications of positively charged amino acids in these proteins. The data obtained are compatible with the hypothesis that lactoferrin and other proteins with similarly high affinity for hepatic heparan sulfate exert their negative effect on iron uptake by preventing transferrin binding to the proteoglycan. The possibility is thus raised that the large number of low-affinity transferrin binding sites reported by earlier investigators for the liver may be heparan sulfate molecules.
Hu
W L
WL
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Regoeczi
E
E
Chindemi
P A
PA
Bolyos
M
M
D000818:Animals; D001212:Asialoglycoproteins / Q000378:metabolism*; D002417:Cattle; D005260:Female; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000378:metabolism; D007501:Iron / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007781:Lactoferrin / Q000494:pharmacology*; D007784:Lactoperoxidase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D012709:Serum Albumin / Q000378:metabolism; D014168:Transferrin / Q000031:analogs & derivatives* / Q000378:metabolism*
D001212:Asialoglycoproteins; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D007501:Iron; D007781:Lactoferrin; D007784:Lactoperoxidase; D011509:Proteoglycans; D012709:Serum Albumin; D014168:Transferrin; C017031:asialotransferrins