Abstract
Recently we described the specific inhibitory action of lactoferrin on chylomicron remnant (CR) uptake into the intact rat liver. Injection of lactoferrin but not transferrin (7 mg/100 g animal weight) together with radiolabelled CR inhibits in vivo uptake into liver by 50%. No inhibition of uptake into spleen was observed1. We demonstrated, that inhibition of uptake is directly connected to endocytosis, since endosomes purified by zonal rotor sucrose gradient centrifugation lack CR-radioactivity almost completely, when prepared from livers of rats that have been injected lactoferrin prior to labelled CR. The radioactivity associated with the liver in the presence of lactoferrin is exclusively located in compartments with a higher density, presumably plasma membranes or associated with endothelial cells. CR do not interact with lactoferrin and are processed normally by lipoprotein lipase in the presence of lactoferrin. Inhibition therefore takes place at an early step of the endocytotic uptake mechanism of CR located on the liver cell plasma membrane. Endocytosis is not blocked totally, as lactoferrin is taken up into endosomes. In addition, in vivo as well as in tissue culture we observed inhibition of CR uptake only and no effect was seen on receptor mediated LDL uptake or uptake of asialoorosomucoid2.
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References
Huettinger M, Retzek H, Eder M, Goldenberg H. Characteristics of chylomicron remnant uptake into rat liver. Clin Biochem. 1988; 21: 87–92
Huettinger M, Rctzek H, Hermann M, Goldenberg H. Lactoferrin specifically inhibits endocytosis of chylomicron remnants but not alpha-macroglobulin. J. Biol. Chem. 1992; 267: 18551–18557
Brown M, Herz J, Goldstein J. Calcium cages. acid baths and recycling receptors. Nature 1997; 388: 629–630
Cardin AD, Demeter DA, Weintraub HJ, Jackson RL. Molecular design and modeling of protein-heparin interactions. Meth. Enzymol. I99I: 203: 556–583
Mann DM, Romm E, Migliorini M. Delineation of the glycosaminoglycan-binding site in the human inflammatory response protein lactoferrin. J. Biol. Chem. 1994; 269: 23661–23667
Ji ZS, Fazio S, Lee YL, Mahley RW. Secretion-Capture Role for Apolipoprotein-E in Remnant Lipoprotein Metabolism Involving Cell Surface Heparan Sulfate Proteoglycans. J. Biol. Chem. 1994; 269: 2764–2772
Morwald S, Yamazaki H, Bujo H, et al. A novel mosaic protein containing LDL receptor elements is highly conserved in humans and chickens. Arter. Thromb. Vas. Biol. 1997; 17: 996–1002.
Nimpf J, Stifani S, Bilous PT, Schneider WJ. The Somatic Cell-Specific Low Density Lipoprotein Receptor-Related Protein of the Chicken–Close Kinship to Mammalian Low Density Lipoprotein Receptor Gene Family Members. J. Biol. Chem. 1994; 269: 212–219
Bujo H, Hermann M, Lindstedt KA, Nimpf J, Schneider WJ. Low density lipoprotein receptor gene family members mediate yolk deposition J. Nutr. 1997;127 Supplement:S80l—S804.
Bujo H, Hermann M, Schneider WJ, Nimpf J. A new branch of the LDL-receptor family tree: VLDL-receptors. Z. Gastroenterol. 1996;34 Suppl 3: 124–126
Novak S, Hiesberger T, Schneider WJ, Nimpf J. A new low density lipoprotein receptor homologue with 8 ligand binding repeats in brain of chicken and mouse. J. Biol. Chem. 1996; 271: 11732–11736
Hiesberger T, Hermann M, Jacobsen L. et al. The chicken oocyte receptor for yolk precursors as a model for studying the action of receptor-associated protein and lactoferrin. J. Biol. Chem. 1995; 270: 18219–18226
Bellosta S, Nathan BP, Orth M, Dong LM, Mahley RW, Pitas RE. Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth. J. Biol. Chem. 1995; 270: 27063–27071
Rebeck GW, Harr SD, Strickland DK. Hyman BT. Multiple, diverse senile plaque-associated proteins are ligands of an apolipoprotein E receptor. the alpha 2-macroglobulin receptor/low-density-lipoprotein receptor-related protein. Ann. Neurol. 1995; 37: 211–217
Weisgraber KH, Roses AD, Strittmatter WJ. The role of apolipoprotein E in the nervous system. Curr. Opin. Lipidol. 1994; 5: 110–116
Lippa CF. Smith TW, Saunders AM, Hulette C, Pulaski Salo D, Roses AD. Apolipoprotein E-epsilon 2 and Alzheimer’s disease: genotype influences pathologic phenotype. Neurology 1997; 48: 515–519
Gocdert M, Strittmatter WJ, Roses AD. Alzheimer’s disease: Risky apolipoprotein in brain. Nature 1994; 372: 45–46
Corder EH, Saunders AM, Strittmatter WJ, et al. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 1993; 261: 921–923
Strittmatter WJ, Saunders AM, Schmechel D, et al. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Natl. Acad. Sei. (U S A) 1993; 90: 1977–1981
Schmidt AM, Mora R, Cao R, et al. The endothelial cell binding site for advanced glycation end products consists of a complex: an integral membrane protein and a lactoferrin-like polypeptide. J. Biol. Chem. 1994; 269: 9882–9888
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Huettinger, M., Meilinger, M., Gschwentner, C., Lassmann, H. (1998). The LDL-Receptor Family. In: Spik, G., Legrand, D., Mazurier, J., Pierce, A., Perraudin, JP. (eds) Advances in Lactoferrin Research. Advances in Experimental Medicine and Biology, vol 443. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9068-9_13
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DOI: https://doi.org/10.1007/978-1-4757-9068-9_13
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