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Inactivation of GM 1 ‐ganglioside β‐galactosidase by a specific inhibitor: A model for ganglioside storage disease
Author(s) -
Singer Harvey S.,
Tiemeyer Michael,
Slesinger Paul A.,
Sinnott Michael L.
Publication year - 1987
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410210514
Subject(s) - ganglioside , choline acetyltransferase , enzyme , lactate dehydrogenase , biochemistry , lysosomal storage disease , in vitro , biology , enzyme assay , chemistry , microbiology and biotechnology , endocrinology , central nervous system
This study was designed to establish an in vitro model with biochemical and morphological similarities to the human neurodegenerative disease GM 1 gangliosidosis. Utilizing a specific inactivator of the lysosomal enzyme GM 1 ‐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 GM 1 ‐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.