Disease relevance of LTF

• The peptide domain of salivary agglutinin responsible for its interaction with cell surface protein antigen (PAc) of Streptococcus mutans or bovine lactoferrin was found in the same peptide, scavenger receptor cysteine-rich domain peptide 2 (SRCRP2) [1].
• In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts [2].
• Although some researches suggest that trace metals, including iron, can be associated with dental caries, the function of salivary iron and lactoferrin in the human oral cavity remains unclear [3].
• The most effective inhibitory activity of Lf was seen against E. coli and P. aeruginosa [4].
• The antibacterial effect of lactoferrin (Lf) was tested on isolates of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and coagulase-negative staphylococci (CNS) as well as on Pseudomonas aeruginosa (P. aeruginosa) and Klebsiella pneumoniae (K. pneumoniae), originally isolated from bovine mastitis [4].
• Lactoferrin could be potentially useful for the treatment of oxidative stress-induced liver diseases [5].

Psychiatry related information on LTF

• Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats [6].
• Lactoferrin (LF) is a multifunctional glycoprotein, which plays an important role in immune regulation and defense mechanisms against bacteria, fungi, and viruses [7].

High impact information on LTF

• This, together with competition observed between lactoferrin and lactoperoxidase on one hand and 2Fe-transferrin and lactoferrin on the other for transfer to bile, suggests that lactoferrin is routed through the hepatocyte in vesicles [8].
• Bovine lactoferricin (LfcinB) is a peptide fragment of iron- and heparin-binding lactoferrin obtained from cow's milk [9].
• Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein [10].
• Surface plasmon resonance analysis indicated that bovine lactoferrin binds more strongly to salivary agglutinin, especially to high molecular mass glycoprotein, which is a component of the agglutinin, than to recombinant PAc [11].
• This lactoferrin-mediated HbR release was inhibited by the cysteine proteinase inhibitors effective to the cysteine proteinases of P. gingivalis [12].

Chemical compound and disease context of LTF

• Lactoferrin inhibits HIV-1 replication in vitro and exhibits synergy when combined with zidovudine [13].
• We recently demonstrated that lactoferrin, an antimicrobial glycoprotein, can inhibit adenovirus infection by competing for common glycosaminoglycan receptors [14].
• The cell envelopes of Salmonella typhimurium 395MS with smooth lipopolysaccharide (LPS) and its five isogenic rough mutants revealed 38-kDa porin proteins as peroxidase-labeled-Lf-reactive components in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (ligand blot) analysis [15].
• The bovine lactoferrin molecule and relatively long lactoferrin fragments containing residues 473 to 538 strongly inhibited adherence of Streptococcus mutans to saliva-coated hydroxyapatite beads [16].
• We investigated the effect of lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats [17].

Biological context of LTF

• Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70% [2].
• Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth [2].
• A peptide domain of bovine milk lactoferrin inhibits the interaction between streptococcal surface protein antigen and a salivary agglutinin peptide domain [1].
• Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo [2].
• Several peptides sharing high sequence homology with lactoferricin B (Lf-cin B) were generated from bovine lactoferrin (Lf) with recombinant chymosin [18].

Anatomical context of LTF

• Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils [2].
• Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 microg/ml) [2].
• Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis [2].
• In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 microg/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand [2].
• Similarly, lactoferrin stimulated proliferation of primary chondrocytes [2].

Associations of LTF with chemical compounds

• LfcinB is a 25-residue antimicrobial peptide released by pepsin cleavage of lactoferrin, an 80 kDa iron-binding glycoprotein with many immunologically important functions [19].
• We found new inhibitory function of lactoferrin and beta-casein in milk against cysteine proteases using reverse zymography [20].
• By looking at the X-ray structure of Lf (PDB ID code: 1BLF) we can locate two water oxygens at 3.95 and 4.27 A from each Fe(III), respectively [21].
• The bovine lactoferrin catalytic activity is irreversibly inhibited by the serine-protease inhibitors PMSF and Pefabloc [22].
• NH2-terminal sequence analysis indicated that the approximately 35-kDa protein was novel, whereas the NH2-terminal sequence of the approximately 80-kDa protein was identical to that of lactoferrin [23].

Physical interactions of LTF

• IGFBP-3 binds to membrane proteins of bovine mammary tissue; an IGFBP-3 binding protein has been identified as bovine lactoferrin [24].
• Lactoferrin binding to heparan sulfate proteoglycans and the LDL receptor-related protein. Further evidence supporting the importance of direct binding of remnant lipoproteins to HSPG [25].

Regulatory relationships of LTF

• Natural bovine lactoferrin inhibited oxidation in buffered corn oil emulsions and lecithin liposome systems at pH 6.6 and 50 degrees C. The antioxidant activity increased with lactoferrin concentration in both phosphate- and Tris-buffered emulsions, but not in both buffered liposome systems [26].

Other interactions of LTF

• The associations between the combined genotypes DGAT1/LTF and DGAT1/LEPTIN analyzed traits are presented as examples.The microarray based on APEX (Arrayed Primer Extension) is a fast and reliable method for multiple SNP analysis of potential application in marker-assisted selection [27].
• Appearance of both IGFBP-3 and lactoferrin in conditioned media of primary cultures of bovine mammary cells was stimulated by all trans retinoic acid (atRA) [24].
• These findings reveal a novel role for lactoferrin, suggesting that lactoferrin is critically involved in the regulation of the IGF system during the involution period [24].
• Down-regulation of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced CYP1A2 expression is associated with bovine lactoferrin inhibition of MeIQx-induced liver and colon carcinogenesis in rats [28].
• A clear inflammatory response was shown by a significant (P < 0.05), dose dependent, increase of lactoferrin and IL-8 secretion within 24h in response to S. aureus or LPS [29].

Analytical, diagnostic and therapeutic context of LTF

• These peptides were isolated in a single step from chymosin-hydrolyzed Lf by membrane ion-exchange chromatography and were purified by reverse-phase high-pressure liquid chromatography (HPLC) [18].
• In TUNEL and DNA fragmentation assays, lactoferrin decreased apoptosis, induced by serum withdrawal, by up to 70% [30].
• However, lactoferrin did not alter bone resorption in calvarial organ culture, suggesting that it does not influence mature osteoclast function [30].
• 2. A method utilizing heparin-agarose affinity chromatography was more efficient for purifying lactoferrin than a method including gel filtration, ion exchange chromatography and a second gel filtration [31].
• In this study, the promoter fragment of LTF gene containing mutation (G/C) in position +32 has been amplified by PCR followed by genotyping by the SSCP and RFLP method [32].

References