Protective and Antioxidative Effects of GM1 Ganglioside in PC12 Cells Exposed to Hydrogen Peroxide are Mediated by Trk Tyrosine Kinase

Abstract

GM1 ganglioside was found to increase the survival of PC12 cells exposed to H(2)O(2), its action was blocked by Trk tyrosine kinase inhibitor K-252a. Thus, the inhibition of H(2)O(2) cytotoxic action by GM1 constituted 52.8 +/- 4.3%, but in the presence of 1.0 microM K-252a it was only 11.7 +/- 10.8%, i.e. the effect of GM1 became insignificant. Exposure to GM1 markedly reduced the increased accumulation of reactive oxygen species (ROS) and diminished the inactivation of Na(+),K(+)-ATPase induced in PC12 cells by H(2)O(2), but in the presence of K-252a GM1 did not change these metabolic parameters. The inhibitors of extracellular signal-regulated protein kinase, phosphatidyl inositol 3-kinase and protein kinase C decreased the effects of GM1. A combination of these protein kinase inhibitors reduced inhibition of H(2)O(2) cytotoxic action by GM1 to the larger extent than each of the inhibitors and practically abolished the ability of GM1 to decrease H(2)O(2)-induced ROS accumulation. The protective and antioxidative effects of GM1 in PC12 cells exposed to H(2)O(2) appear to be mediated by activation of Trk receptor tyrosine kinase and the protein kinases downstream from this enzyme.

Protective effects of exogenous gangliosides on ROS-induced changes in human spermatozoa

“…35 Their mode of action varies in different cell types, including altering the activity of several enzymes and specific proteins, [36][37][38][39][40] membrane stabilisation and fluidity, 34,35 scavenging hydroxyl radicals. 41 Even if there were a consensus on the protective effects of gangliosides against cellular damage, the mechanism(s) underlying these effects and the models in which gangliosides are protective would still require precise evaluation.…”

Antiapoptotic effect of gangliosides on PC12 cells exposed to bacterial lipopolysaccharide

“…Symbols as in Fig. 2. of nerve cells or neuronal cell lines under exposure to excitatory amino acids [9,17,18], amyloid beta-peptide [19,20], hydrogen peroxide [10,19] or long-term effect of a serum-free medium [21,22]. However, we could not find any data on the protective effect of gangliosides on nerve cells or neuronal cell lines under exposure to LPS.…”

“…From the natural neuroprotectors, most important are gangliosides localized in animals mainly in the membranes of the brain nerve cells. Gangliosides were shown to increase the viability of nerve cells in culture and in vivo (brain neurons) under the effect of excitatory amino acids or other toxins [9][10][11]. In addition, gangliosides were reported to prevent the intestinal mucosal cell death caused by the toxic effect of LPS [12], although we failed to find any literary data on the protective effect of gangliosides against the toxic influence of LPS on nerve cells and neuronal cell lines.…”

“…The mixture of chloroform, methanol and water in ratio of 65:25:4 (by volume) and 65:35:7 (by volume) was used as a solvent. The isolated GD1a and GM1 preparations were purified as described elsewhere [9]. The purity of the GD1a and GM1 preparations used in the study was no less than 98%, as evidenced by a thin-layer chromatography on silica gel using HPTLP plates (Merck, Germany).…”

Disialogangliosides and TNFα Alter Gene Expression for Cytokines and Chemokines in Primary Brain Cell Cultures

“…Gangliosides like GM1 characteristic of mature brain cells appear to be neuroprotective by inhibiting the accumulation of reactive oxygen species [47]. By contrast, GD3 may promote the generation of reactive oxygen species that lead to apoptosis [45].…”