HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Inactivation of GM1-ganglioside beta-galactosidase by a specific inhibitor: a model for ganglioside storage disease.

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 beta-galactosidase (beta-D-galactopyranosylmethyl-p-nitrophenyltriazene [beta-GalMNT]) and neuroblastoma X glioma hybrid cells (NG108-15), we suppressed beta-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. beta-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.
AuthorsH S Singer, M Tiemeyer, P A Slesinger, M L Sinnott
JournalAnnals of neurology (Ann Neurol) Vol. 21 Issue 5 Pg. 497-503 (May 1987) ISSN: 0364-5134 [Print] United States
PMID3035998 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Triazenes
  • G(M1) Ganglioside
  • beta-D-galactopyranosylmethyl-4-nitrophenyltriazene
  • Galactosidases
  • acid beta-galactosidase
  • beta-Galactosidase
Topics
  • Brain (enzymology, pathology)
  • Brain Diseases, Metabolic (enzymology, pathology)
  • G(M1) Ganglioside (metabolism)
  • Galactosidases (antagonists & inhibitors)
  • Gangliosidoses (enzymology, pathology)
  • Humans
  • Inclusion Bodies (ultrastructure)
  • Lysosomes (enzymology)
  • Triazenes (pharmacology)
  • beta-Galactosidase (antagonists & inhibitors, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: