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 gan glioside GM1 was shown to protect Ca2+-dependent and Ca2+-independent cyclic nucleotide phosphodiesterase from inactivation caused by lipid peroxidation (LPO) induction. Thus, Ca2+-dependent phosphodiesterase a ctivity decreased to approximately 34% of the initial value following 30 min of LPO induction, but it constituted more than 60% of the contr ol activity if synaptosomes were preincubated with 10(-8)M GM1, the di fference being statistically significant. 10(-6)M alpha-tocopherol had a similar effect. As far as the lipid matrix is concerned, gangliosid es were found to prevent to a great extent malonic dialdehyde (MDA) ac cumulation and to protect polyenoic fatty acids from oxidative destruc tion. The ability of gangliosides to protect phosphodiesterase from in activation caused by LPO induction appears to be owing not only to the inhibition of the accumulation of LPO products, but to the direct act ivation of the enzyme as well, 10(-7)M of ganglioside GM1 having the m aximal activating effect. In contrast to alpha-tocopherol and other an tioxidants reacting directly with free radicals, the inhibitory effect of gangliosides appears to be mediated by signal transduction systems .