Abstract
To elucidate the potential of mammalian milk as to protection of infants from infections, we determined the ganglioside compositions of human, cow and goat milk in relation with cholera toxin and botulinum type A neurotoxin-receptors. Gangliosides accounted for 1 to 2 μmol of lipid-bound sialic acid (LSA) in 100 ml of milk, and GD3 comprised about 69% of LSA in all milk samples. Among the milk samples examined, goat milk was found to contain an amount of gangliosides belonging to the b-pathway representing 15.8% of the total LSA. Accordingly, botulinum neurotoxin bound to GT1b and GQ1b in goat milk, but not to any gangliosides in human or cow milk. On the other hand, GM1, the cholera toxin receptor, was found to be present in all milk samples at concentrations of 0.02% to 0.77% of the total LSA and to be maintained at a relatively constant level in human milk during the postpartum period. Gangliosides from 1 ml of pooled human milk exhibited the ability to attenuate the binding of cholera toxin (30 ng) to GM1 by 93%, and those from 500 μl of goat milk completely inhibited the binding of botulinum type A neurotoxin 1.5 μg to GT1b.
Similar content being viewed by others
References
IUPAC-IUB Commission on Biochemical Nomenclature: The nomenclature of lipids. Eur. J. Biochem. 79, 11–21 (1977)
Svennerholm, L.: Chromatographic separation of human brain gangliosides. J. Neurochem. 10, 613–623 (1963)
Taketani, Y., Oka, T.: Epidermal growth factor stimulates cell proliferation and inhibits functional differentiation of mouse mammary epithelial cells in culture. Endocrinology. 113, 871–877 (1983)
Tsutsumi, O., Oka, T.: Epidermal growth factor deficiency during pregnancy causes abortion in mice. Am. J. Obstet. Gynecol. 156, 241–244 (1987)
Momoeda, M., Momoeda, K., Takamizawa, K., Matsuzawa, A., Hanaoka, K., Taketani, Y., Iwamori, M.: Characteristic expression of GD1 alpha-ganglioside during lactation in murine mammary gland. Biochim. Biophys. Acta 1256, 151–156 (1995)
Furuya, S., Irie, F., Hashikawa, T., Nakazawa, K., Kozakai, A., Hasegawa, A., Sudo, K., Hirabayashi, Y.: Ganglioside GD1 alpha in cerebellar Purkinje cells. Its specific absence in mouse mutants with Purkinje cell abnormality and altered immunoreactivity in response to conjunctive stimuli causing long-term desensitization. J. Biol. Chem. 269, 32418–32425 (1994)
Takamizawa, K., Iwamori, M., Mutai, M., Nagai, Y.: Selective changes in gangliosides of human milk during lactation: a molecular indicator for the period of lactation. Biochim. Biophys. Acta 879, 73–77 (1986)
Vanier, M.T., Holm, M., Mansson, J.E., Svennerholm, L.: The distribution of lipids in the human nervous system-V. Gangliosides and allied neutral glycolipids of infant brain. J. Neurochem. 21, 1375–1384 (1973)
Seyfried, T.N., Bernard, D.J., Yu, R.K.: Cellular distribution of gangliosides in the developing mouse cerebellum: analysis using the staggerer mutant. J. Neurochem. 43, 1152–1162 (1984)
Yu, R.K., Macala, L.J., Taki, T., Weinfield, H.M., Yu, F.S.: Developmental changes in ganglioside composition and synthesis in embryonic rat brain. J. Neurochem. 50, 1825–1829 (1988)
Wolswijk, G.: Strongly GD3+ cells in the developing and adult rat cerebellum belong to the microglial lineage rather than to the oligodendrocyte lineage. Glia. 13, 13–26 (1995)
Iwamori, M.: A new turning point in glycosphingolipid research. Hum. Cell. 18, 117–133 (2005)
Laegreid, A., Otnaess, A.B.: Fuglesang J, Human and bovine milk: comparison of ganglioside composition and enterotoxin-inhibitory activity. Pediatr. Res. 20, 416–421 (1986)
Newburg, D.S.: Human milk glycoconjugates that inhibit pathogens. Curr. Med. Chem. 6, 117–127 (1999)
Richards, R.L., Moss, J., Alving, C.R., Fishman, P.H., Brady, R.O.: Choleragen (cholera toxin): a bacterial lectin, Proc. Natl. Acad. Sci. U.S.A. 76, 1673–1676 (1979)
Fishman, P.H., Moss, J., Richards, R.L., Brady, R.O.: Alving CR, liposomes as model membranes for ligand-receptor interactions: studies with choleragen and glycolipids. Biochemistry 18, 2562–2567 (1979)
Takamizawa, K., Iwamori, M., Mutai, M., Nagai, Y.: Gangliosides of bovine buttermilk. Isolation and characterization of a novel monosialoganglioside with a new branching structure. J. Biol. Chem. 261, 5625–5630 (1986)
Iwamori, M., Iwamori, Y.: Establishment of cells exhibiting mutated glycolipid synthesis from mouse thymus by immortalization with SV-40 virus. Glycoconj. J. 22, 417–425 (2005)
Iwamori, M., Ohta, Y., Uchida, Y., Tsukada, Y.: Arthrobacter ureafaciens sialidase isoenzymes, L, M1 and M2, cleave fucosyl GM1. Glycoconj. J. 14, 67–73 (1997)
Miettinen, T., Takki-Luukkainen, I.T.: Use of butyl acetate in determination of sialic acid. Acta. Chem. Scand. 13, 856–858 (1959)
Iwamori, M., Nagai, Y.: A new chromatographic approach to the resolution of individual gangliosides. Ganglioside mapping. Biochim. Biophys. Acta 528, 257–267 (1978)
Iwamori, M., Sawada, K., Hara, Y., Nishio, M., Fujisawa, T., Imura, H., Nagai, Y.: Neutral glycosphingolipids and gangliosides of bovine thyroid. J. Biochem. (Tokyo) 91, 1875–1887 (1982)
Takamizawa, K., Iwamori, M., Kozaki, S., Sakaguchi, G., Tanaka, R., Takayama, H., Nagai, Y.: TLC immunostaining characterization of Clostridium botulinum type A neurotoxin binding to gangliosides and free fatty acids. FEBS Lett. 201, 229–232 (1986)
Iwamori, M., Hirota, K., Utsuki, T., Momoeda, K., Ono, K., Tsuchida, Y., Okumura, K., Hanaoka, K.: Sensitive method for the determination of pulmonary surfactant phospholipid/sphingomyelin ratio in human amniotic fluids for the diagnosis of respiratory distress syndrome by thin-layer chromatography-immunostaining. Anal. Biochem. 238, 29–33 (1996)
Keenan, T.W., Huang, C.M., Morre, D.J.: Gangliosides: nonspecific localization in the surface membranes of bovine mammary gland and rat liver. Biochem. Biophys. Res. Commun. 47, 1277–1283 (1972)
Patton, S., Keenan, T.W.: The milk fat globule membrane. Biochim. Biophys. Acta 415, 273–309 (1975)
Puente, R., Garcia-Pardo, L.A., Hueso, P.: Gangliosides in bovine milk. Changes in content and distribution of individual ganglioside levels during lactation. Biol. Chem. Hoppe-Seyler 373, 283–288 (1992)
Otnaess, A.B., Laegreid, A., Ertresvag, K.: Inhibition of enterotoxin from Escherichia coli and Vibrio cholerae by gangliosides from human milk. Infect. Immun. 40, 563–569 (1983)
Qureshi, K., Molbak, K., Sandstrom, A., Kofoed, P.E., Rodrigues, A., Dias, F., Aaby, P., Svennerholm, A.M.: Breast milk reduces the risk of illness in children of mothers with cholera: observations from an epidemic of cholera in Guinea–Bissau. Pediatr. Infect. Dis. J. 25, 1163–1166 (2006)
Karlsson, K.A.: Animal glycosphingolipids as membrane attachment sites for bacteria. Annu. Rev. Biochem. 58, 309–350 (1989)
Kracun, I., Rosner, H., Cosovic, C., Stavljenic, A.: Topographical atlas of the gangliosides of the adult human brain. J. Neurochem. 43, 979–989 (1984)
Lorke, D.E., Sonnentag, U., Rosner, H.: Developmental profiles of gangliosides in trisomy 19 mice. Dev. Biol. 142, 194–202 (1990)
Rosenberg, A., Sauer, A., Noble, E.P., Gross, H.J., Chang, R., Brossmer, R.: Developmental patterns of ganglioside sialosylation coincident with neuritogenesis in cultured embryonic chick brain neurons. J. Biol. Chem. 267, 10607–10612 (1992)
Tsuji, S., Arita, M., Nagai, Y.: GQ1b, a bioactive ganglioside that exhibits novel nerve growth factor (NGF)-like activities in the two neuroblastoma cell lines. J. Biochem. (Tokyo). 94, 303–306 (1983)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Iwamori, M., Takamizawa, K., Momoeda, M. et al. Gangliosides in human, cow and goat milk, and their abilities as to neutralization of cholera toxin and botulinum type A neurotoxin. Glycoconj J 25, 675–683 (2008). https://doi.org/10.1007/s10719-008-9128-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-008-9128-6