The protective effect of GD1a ganglioside and inhibitors of nitric oxide synthase after the application of bacterial lipopolysaccharide to PC12 cells

Abstract

Lipopolysaccharide from Escherichia coli, serotype 0111: B4 (LPS), at concentrations of 0.125 and 0.25 mg/mL exhibited toxic effects in cells of the neuronal PC12 line in DMEM medium. Higher concentrations of LPS are necessary to induce the death of PC12 cells in serum-containing medium. The nonspecific inhibitor of nitric oxide synthase (NOS) and the inhibitor of inducible NOS (iNOS) increased the survival of the PC12 cells, whereas an inhibitor of cyclooxygenase 1/2 (COX 1/2) enhanced cell death. We found that GD1a ganglioside at concentrations of 50 and 100 μM increased the survival of PC12 cells in DMEM medium after LPS application and decreased the LPS-induced accumulation of reactive oxygen species. Our data suggest that the activation of NOS and, specifically, iNOS, is involved in the toxic LPS effect in PC12 cells, whereas the activation of COX 1/2 weakens this effect. The protective and antioxidant effects of GD1a ganglioside in PC12 cells after LPS application probably depends on the capability of gangliosides to modify raft structure after their incorporation into membranes and to prevent the activation of TLR receptors in cell membranes.