title: GM1 ganglioside activates ERK1/2 and Akt downstream of Trk tyrosine kinase and protects PC12 cells against hydrogen peroxide toxicity.
abstract: Ganglioside GM1 at micro- and nanomolar concentrations was shown to increase the viability of pheochromocytoma PC12 cells exposed to hydrogen peroxide and diminish the accumulation of reactive oxygen species and oxidative inactivation of Na(+),K(+)-ATPase, the effects of micromolar GM1 being more pronounced than those of nanomolar GM1. These effects of GM1 were abolished by Trk receptor tyrosine kinase inhibitor and diminished by MEK1/2, phosphoinositide 3-kinase and protein kinase C inhibitors. Hydrogen peroxide activates Trk tyrosine kinase; Akt and ERK1/2 are activated downstream of this protein kinase. GM1 was found to activate Trk receptor tyrosine kinase in PC12 cells. GM1 (100 nM and 10 µM) increased the basal activity of Akt, but did not change Akt activity in cells exposed to hydrogen peroxide. Basal ERK1/2 activity in PC12 cells was increased by GM1 at a concentration of 10 µM, but not at nanomolar concentrations. Activation of ERK1/2 by hydrogen peroxide was enhanced by GM1 at a concentration of 10 µM and to a lesser extent at a concentration of 100 nM. Thus, the protective and metabolic effects of GM1 ganglioside on PC12 cells exposed to hydrogen peroxide appear to depend on the activation of Trk receptor tyrosine kinase and downstream activation of Akt and ERK1/2.
authors.affiliation: Department of Comparative Neurochemistry, I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Thorez Avenue, 44, Saint Petersburg, 194223, Russian Federation.
authors.forename: Irina O
authors.initials: IO
authors.lastname: Zakharova
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Sokolova
authors.forename: Yulia A
authors.initials: YA
authors.lastname: Vlasova
authors.forename: Victor V
authors.initials: VV
authors.lastname: Furaev
authors.forename: Maria P
authors.initials: MP
authors.lastname: Rychkova
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Avrova
mesh_terms: D000818:Animals; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism
chemical_list: D005677:G(M1) Ganglioside; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3