Ganglioside GM1 protects cAMP 3'5':phosphodiesterase from inactivation caused by lipid peroxidation in brain synaptosomes of rats.

The preincubation of synaptosomes with nanomolar concentrations of ganglioside GM1 was shown to protect Ca(2+)-dependent and Ca(2+)-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca(2+)-dependent phosphodiesterase activity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the control activity if synaptosomes were preincubated with 10(-8)M GM1, the difference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosides were found to prevent to a great extent malonic dialdehyde (MDA) accumulation and to protect polyenoic fatty acids from oxidative destruction. The ability of gangliosides to protect phosphodiesterase from inactivation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct activation of the enzyme as well, 10(-7) M of ganglioside GM1 having the maximal activating effect. In contrast to alpha-tocopherol and other antioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems.