GANGLIOSIDE-DEPENDENT FACTOR INHIBITING LIPID-PEROXIDATION IN SYNAPTOSOMAL MEMBRANES

Experiments in vitro have shown that if standard systems are used to generate active forms of oxygen, significantly less accumulation of lipid peroxidation (LPO) products takes place in the plasma membranes than in the intracellular membranes (fraction of microsomes and mitochondria) [9]. Among the possible causes of resistance of the plasma membranes to LPO inducers at least three may be mentioned: the higher level of saturation of the phospholipids of these membranes and the fact that they contain predominantly glycolipids with a higher degree of saturation [2], the higher cholesterol concentration [3], and effective inhibition of LPO by an enzymic mechanism, coupled with activation of protein kinase C [10]. Gangliosides not only largely determine the structural and functional organization of the plasma membranes of cells, and play an essential role in processes of intercellular interaction and reception of biologically active substances, but they also take part in the regulation of differentiation, plasticity, and regeneration of nerve cells. However, the biochemical mechanisms of the neuronotrophic and neuroregenerative effect of gangliosides have not been elucidated [1]. It has recently been shown that gangliosides are modulators of the activity of various protein kinases, including protein kinase C [12]. With these considerations in mind, and also the fact that gangliosides are localized mainly in the outer monolayer of the plasma membranes of synaptosomes, where they may account for up to 10-15 moles % of the total lipids [4], the investigation described below was carried out to study the action of exogenous monosialoganglioside GM1 (accounting for about 30% of the total mammalian brain gangliosides) on synaptosomes of the rat brain.