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.

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This study focuses on the potential involvement of carnitine palmitoyltransferase (CPT) on the phospholipid and triglyceride fatty acid turnover in neurons. This category of enzymes, which has been identified in several rat brain tissues, is well known for its role in modulating cellular fatty acid oxidation. Neuronal cell cultures from rat brain cortex incorporated radioactive palmitate or oleate into phospholipids and triglycerides. The largest fraction of radioactive fatty acids was recovered in phosphatidylcholine followed by triglycerides and, to a lesser extent, phosphatidylethanolamine. CPT activity measured in neuronal lysates obtained from neurons treated with 40 pM 2-tetradecylglycidic acid (TDGA) was almost completely abolished. Furthermore, between 2 and 10 pM TDGA CPT

The composition and content of gangliosides from rat-brain microsomal, synaptosomal, mitochondrial and myelin fractions were studied. Outer membranes of synaptosomes were also isolated, separated into subfractions and investigated. Of all the fractions studied the outer membranes of synaptosomes are richest in gangliosides, in one of their subfractions the concentration of gangliosides per mg of protein is five times higher than in the homogenate. Microsomes are rich in gangliosides as well, but to a lesser degree, whereas the mitochondrial fraction contains considerably smaller amounts of gangliosides per mg of protein than does the homogenate. The ganglioside pattern of outer membranes of synaptosomes and of their subfractions is somewhat different from that of the homogenate; the outer membranes contain approximately one-third less monosialogangliosides. On the contrary a very high content of monosialogangliosides is characteristic of the ganglioside pattern of the myelin fraction. In this fraction monosialoganglioside G,, (nomenclature of Svennerholm, 1963) constitutes 60-63 per cent of ganglioside sialic acid, or 75-80 molar per cent of gangliosides, the content of di-and trisialogangliosides being much lower than in other fractions. Fatty acid and long chain base composition of gangliosides from synaptosomal and microsomal fractions and homogenate is very similar, almost identical. In gangliosides from myelin fractions the relaitve content of palmitic and monoenoic acids is higher and that of arachinic acid and C20-sphingosine-lower than in other fractions studied. The difference in ganglioside composition of synaptosomes and their outer membranes and on the other hand of myelin appears to reflect the difference in ganglioside composition of neuronal and oligodendroglial plasma membranes.GANGLIOSIDES are localized mainly in cell membranes of the nervous tissue especially in the outer membranes of synaptosomes and in microsomes (WHITTAKER, 1965; LAPETINA, SOTO and DE ROBERTIS, 1967;WIEGANDT, 1967;TROTTER and BURTON, 1969). The enzymes of their metabolism appear to have the same localization (TETTA-MANTI, LOMBARDO, PRETI and DI DONATO, 1969; OHMAN, 1971 ; DI CESARE and