Inactivation of GM1-ganglioside ?-galactosidase by a specific inhibitor: A model for ganglioside storage disease

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Abstract
This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM1-ganglioside β-galactosidase (β-D-galactopyranosylmethyl-p-nitrophenyltriazene [β-GalMNT]) and neuroblastoma X glioma hybrid cells (NG108–15), we suppressed β-galactosidase activity for up to 72 hours. Coincidental with suppression of this enzyme to levels less than 1% of control, we found up to a nine-fold accumulation of its substrate, the GM1-ganglioside, and the ultrastructural appearance of membranous cytoplasmic bodies. β-GalMNT treatment suppressed growth but had little effect on the specific activity of choline acetyltransferase, lactate dehydrogenase, or other lysosomal enzymes including galactosylceramidase. This model should permit studies of the neurophysiological effects of increased ganglioside accumulation and their reversibility.