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Gene Review

LTF  -  lactotransferrin

Bos taurus

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Disease relevance of LTF


Psychiatry related information on LTF


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


Biological context of LTF


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


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


  1. A peptide domain of bovine milk lactoferrin inhibits the interaction between streptococcal surface protein antigen and a salivary agglutinin peptide domain. Oho, T., Bikker, F.J., Nieuw Amerongen, A.V., Groenink, J. Infect. Immun. (2004) [Pubmed]
  2. Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Cornish, J., Callon, K.E., Naot, D., Palmano, K.P., Banovic, T., Bava, U., Watson, M., Lin, J.M., Tong, P.C., Chen, Q., Chan, V.A., Reid, H.E., Fazzalari, N., Baker, H.M., Baker, E.N., Haggarty, N.W., Grey, A.B., Reid, I.R. Endocrinology (2004) [Pubmed]
  3. Both lactoferrin and iron influence aggregation and biofilm formation in Streptococcus mutans. Berlutti, F., Ajello, M., Bosso, P., Morea, C., Petrucca, A., Antonini, G., Valenti, P. Biometals (2004) [Pubmed]
  4. Antibacterial effect of bovine lactoferrin against udder pathogens. Kutila, T., Pyörälä, S., Saloniemi, H., Kaartinen, L. Acta Vet. Scand. (2003) [Pubmed]
  5. Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats. Tsubota, A., Yoshikawa, T., Nariai, K., Mitsunaga, M., Yumoto, Y., Fukushima, K., Hoshina, S., Fujise, K. J. Hepatol. (2008) [Pubmed]
  6. Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats. Kamemori, N., Takeuchi, T., Hayashida, K., Harada, E. Brain Res. (2004) [Pubmed]
  7. Lactoferrin and lactoferricin inhibit Herpes simplex 1 and 2 infection and exhibit synergy when combined with acyclovir. Andersen, J.H., Jenssen, H., Gutteberg, T.J. Antiviral Res. (2003) [Pubmed]
  8. Transport of lactoferrin from blood to bile in the rat. Regoeczi, E., Chindemi, P.A., Hu, W.L. Hepatology (1994) [Pubmed]
  9. Bovine lactoferricin inhibits basic fibroblast growth factor- and vascular endothelial growth factor165-induced angiogenesis by competing for heparin-like binding sites on endothelial cells. Mader, J.S., Smyth, D., Marshall, J., Hoskin, D.W. Am. J. Pathol. (2006) [Pubmed]
  10. Identification of a lactoferrin-derived peptide possessing binding activity to hepatitis C virus E2 envelope protein. Nozaki, A., Ikeda, M., Naganuma, A., Nakamura, T., Inudoh, M., Tanaka, K., Kato, N. J. Biol. Chem. (2003) [Pubmed]
  11. Inhibitory effect of bovine milk lactoferrin on the interaction between a streptococcal surface protein antigen and human salivary agglutinin. Mitoma, M., Oho, T., Shimazaki, Y., Koga, T. J. Biol. Chem. (2001) [Pubmed]
  12. Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis. Shi, Y., Kong, W., Nakayama, K. J. Biol. Chem. (2000) [Pubmed]
  13. Lactoferrin inhibits HIV-1 replication in vitro and exhibits synergy when combined with zidovudine. Viani, R.M., Gutteberg, T.J., Lathey, J.L., Spector, S.A. AIDS (1999) [Pubmed]
  14. Bovine lactoferrin inhibits adenovirus infection by interacting with viral structural polypeptides. Pietrantoni, A., Di Biase, A.M., Tinari, A., Marchetti, M., Valenti, P., Seganti, L., Superti, F. Antimicrob. Agents Chemother. (2003) [Pubmed]
  15. Relationship between antibacterial activity and porin binding of lactoferrin in Escherichia coli and Salmonella typhimurium. Naidu, S.S., Svensson, U., Kishore, A.R., Naidu, A.S. Antimicrob. Agents Chemother. (1993) [Pubmed]
  16. Functional domain of bovine milk lactoferrin which inhibits the adherence of Streptococcus mutans cells to a salivary film. Oho, T., Mitoma, M., Koga, T. Infect. Immun. (2002) [Pubmed]
  17. Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. Togawa, J., Nagase, H., Tanaka, K., Inamori, M., Umezawa, T., Nakajima, A., Naito, M., Sato, S., Saito, T., Sekihara, H. Am. J. Physiol. Gastrointest. Liver Physiol. (2002) [Pubmed]
  18. Antibacterial activity in bovine lactoferrin-derived peptides. Hoek, K.S., Milne, J.M., Grieve, P.A., Dionysius, D.A., Smith, R. Antimicrob. Agents Chemother. (1997) [Pubmed]
  19. Three-dimensional solution structure of lactoferricin B, an antimicrobial peptide derived from bovine lactoferrin. Hwang, P.M., Zhou, N., Shan, X., Arrowsmith, C.H., Vogel, H.J. Biochemistry (1998) [Pubmed]
  20. New functions of lactoferrin and beta-casein in mammalian milk as cysteine protease inhibitors. Ohashi, A., Murata, E., Yamamoto, K., Majima, E., Sano, E., Le, Q.T., Katunuma, N. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. 1H NMR relaxometric characterization of bovine lactoferrin. Fasano, M., Fanali, G., Polticelli, F., Ascenzi, P., Antonini, G. J. Inorg. Biochem. (2004) [Pubmed]
  22. Proteolytic activity of bovine lactoferrin. Massucci, M.T., Giansanti, F., Di Nino, G., Turacchio, M., Giardi, M.F., Botti, D., Ippoliti, R., De Giulio, B., De Giulio, B., Siciliano, R.A., Siciliano, R., Donnarumma, G., Valenti, P., Bocedi, A., Polticelli, F., Ascenzi, P., Antonini, G. Biometals (2004) [Pubmed]
  23. Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. Schmidt, A.M., Vianna, M., Gerlach, M., Brett, J., Ryan, J., Kao, J., Esposito, C., Hegarty, H., Hurley, W., Clauss, M. J. Biol. Chem. (1992) [Pubmed]
  24. Insulin-like growth factor (IGF) system in the bovine mammary gland and milk. Baumrucker, C.R., Erondu, N.E. Journal of mammary gland biology and neoplasia. (2000) [Pubmed]
  25. 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. Ji, Z.S., Mahley, R.W. Arterioscler. Thromb. (1994) [Pubmed]
  26. Effect of lactoferrin on oxidative stability of corn oil emulsions and liposomes. Huang, S.W., Satué-Gracia, M.T., Frankel, E.N., German, J.B. J. Agric. Food Chem. (1999) [Pubmed]
  27. Associations Between Milk Performance Traits in Holstein Cows and 16 Candidate SNPs Identified by Arrayed Primer Extension (APEX) Microarray. Kamiński, S., Brym, P., Ruść, A., Wójcik, E., Ahman, A., Mägi, R. Anim. Biotechnol. (2006) [Pubmed]
  28. 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. Fujita, K., Ohnishi, T., Sekine, K., Iigo, M., Tsuda, H. Jpn. J. Cancer Res. (2002) [Pubmed]
  29. Cryopreserved bovine mammary cells to model epithelial response to infection. Wellnitz, O., Kerr, D.E. Vet. Immunol. Immunopathol. (2004) [Pubmed]
  30. Lactoferrin promotes bone growth. Cornish, J. Biometals (2004) [Pubmed]
  31. Purification and characterization of bovine lactoferrin from secretions of the involuting mammary gland: identification of multiple molecular weight forms. Rejman, J.J., Hegarty, H.M., Hurley, W.L. Comp. Biochem. Physiol., B (1989) [Pubmed]
  32. Single nucleotide polymorphism in the promoter region of the lactoferrin gene and its associations with milk performance traits in Polish Holstein-Friesian cows. Kaminski, S., Ole??ski, K., Brym, P., Malewski, T., Sazanov, A.A. Genetika (2006) [Pubmed]
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