title: GM1 and GD1a gangliosides modulate toxic and inflammatory effects of E. coli lipopolysaccharide by preventing TLR4 translocation into lipid rafts.
abstract: Exogenous gangliosides are known to inhibit the effects of Escherichia coli lipopolysaccharide (LPS) in different cells exhibiting anti-inflammatory and immunosuppressive activities. The mechanisms underlying ganglioside action are not fully understood. Because LPS recognition and receptor complex formation occur in lipid rafts, and gangliosides play a key role in their maintenance, we hypothesize that protective effects of exogenous gangliosides would depend on inhibition of LPS signaling via prevention of TLR4 translocation into lipid rafts. The effect of GM1 and GD1a gangliosides on LPS-induced toxic and inflammatory reactions in PC12 cells, and in epithelial cells isolated from the frog urinary bladder, was studied. In PC12 cells, GD1a and GM1 significantly reduced the effect of LPS on the decrease of cell survival and on stimulation of reactive oxygen species production. In epithelial cells, gangliosides decreased LPS-stimulated iNOS expression, NO, and PGE2 production. Subcellular fractionation, in combination with immunoblotting, showed that pretreatment of cells with GM1, GD1a, or methyl-β-cyclodextrin, completely eliminated the effect of LPS on translocation of TLR4 into lipid rafts. The results are consistent with the hypothesis that ganglioside-induced prevention of TLR4 translocation into lipid rafts could be a mechanism of protection against LPS in various cells.
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Nikolaeva
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Lubov
authors.initials: L
authors.lastname: Bayunova
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Sokolova
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Vlasova
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Bachteeva
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Avrova
authors.affiliation: I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, 194223 Saint Petersburg, Russia. Electronic address: rimma_parnova@mail.ru.
authors.forename: Rimma
authors.initials: R
authors.lastname: Parnova
mesh_terms: D000818:Animals; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry; D005677:G(M1) Ganglioside / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects* / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D061251:Primary Cell Culture; D021381:Protein Transport; D011896:Rana temporaria; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C064020:ganglioside GD1alpha; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone
keywords: Frog urinary bladder epithelial cells; Ganglioside; Lipid raft; Lipopolysaccharide; PC12 cells; TLR4