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Fluorescence Polarization Analysis, Lipid Composition, and Na + , K + ‐ATPase Kinetics of Synaptosomal Membranes in Feline GM 1 and GM 2 Gangliosidosis
Author(s) -
Wood Philip A.,
McBride Michael R.,
Baker Henry J.,
Christian Samuel T.
Publication year - 1985
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1985.tb12909.x
Subject(s) - chemistry , membrane , phospholipid , ganglioside , cats , catabolism , biochemistry , synaptosome , atpase , kinetics , enzyme , endocrinology , medicine , biology , physics , quantum mechanics
Neurochemical studies were performed on synaptosomal membranes from cats with GM 1 or GM 2 gangliosidosis to examine possible mechanisms of neuronal dysfunction in these disorders. The basic hypothesis tested was that deficient ganglioside catabolism causes increased ganglioside content of synaptosomal plasma membrane which in turn disrupts normal function. Fluidity characteristics of synaptosomal membranes were examined using fluorescence polarization. Results showed markedly reduced membrane fluidity in both GM 1 and GM 2 gangliosidosis. These results were supported by a second study which revealed that isolated synaptosomal membranes of GM 1 gangliosidosis cats had a 24‐fold increase in total ganglioside content caused predominantly by excess GM 1 , a 2.3‐fold increased cholesterol content, and a 1.4‐fold increased phospholipid content. Finally, kinetic analysis of synaptosomal plasma membrane Na + , K + ‐ATPase from cats with GM 1 gangliosidosis showed negligible differences in kinetic parameters compared with controls. Thus, the enzyme appeared protected from the global membrane changes in fluidity and composition. These observations provide evidence for a pathogenetic mechanism of neuronal dysfunction in the gangliosidoses while demonstrating protection of certain vital functional components, such as Na + , K + ‐ATPase.