Neuroprotective Effect of Ganglioside GM1 on the Cytotoxic Action of Hydrogen Peroxide and Amyloid β-peptide in PC12 cells

Abstract

Ganglioside GM1 was shown to increase the viability of PC12 cells exposed to hydrogen peroxide or amyloid beta-peptide (Abeta(25-35)). The PC12 cells transfected with mutant gene (expressing APP(SW)) were found to be more sensitive to oxidative stress than the cells transfected with wild type gene (expressing APP(WT)) or vector-transfected cells, GM1 being effective in enhancing the viability of the cells transfected with mutant gene. The exposure to hydrogen peroxide or Abeta(25-35) results in a partial inactivation of Na(+),K(+)-ATPase in PC12 cells, H(2)O(2) increases MDA accumulation in these cells. But these effects could be partially prevented or practically abolished by GM1 ganglioside. In the presence of the inhibitor of tyrosine kinase of Trk receptors (K-252a) the protective and metabolic effects of GM1 on PC12 cells in conditions of oxidative stress caused by hydrogen peroxide are not observed or are markedly diminished.

GM1 Ganglioside Inhibits β‐Amyloid Oligomerization Induced by Sphingomyelin

“…Our findings suggest that decreasing GM 1 levels (reported to occur with age)7, 8a, 19 could lead to reduced protection from the oligomerization‐triggering effect of Sph and thus contribute to spark AD's onset. The provided molecular insights support reports on the neuroprotective effects of GM 1 in cell cultures and rat models of AD 9, 20. Our results help to rationalize data found in vivo and can help build the basis for a better understanding of amyloid diseases.…”

Thematic Review Series: Sphingolipids. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease—a review

“…Interestingly, GM1 has been shown to increase the viability of PC12 cells exposed to hydrogen peroxide or Ab25-35 (15). PC12 cells transfected with a mutant gene expressing the Swedish APP double mutation were more sensitive to oxidative stress than cells transfected with wild-type APP or vector-transfected cells.…”

“…Gangliosides are also known to provide a neuroprotective role in in vivo and in vitro models of neuronal injury (14). The mechanisms of the neuroprotective effect of GM1 and related gangliosides, however, are still obscure (15).…”

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

“…/ calmodulin-dependent protein kinase II [21], protein kinase C (PKC) [22], and of other enzymes. But there are only few studies trying to reveal the main signaling systems responsible for the protective effect of GM1 [16,20,23,24]. The Trk tyrosine kinase inhibitor K-252a was found to decrease the ability of GM1 to prevent the death of PC12 cells in serum-free medium [16] or exposed to hydrogen peroxide [24].…”