Inhibition of calcium uptake via the sarco/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin

The Journal of Biological Chemistry
Dori PelledAnthony H Futerman

Abstract

Gangliosides are found at high levels in neuronal tissues where they play a variety of important functions. In the gangliosidoses, gangliosides accumulate because of defective activity of the lysosomal proteins responsible for their degradation, usually resulting in a rapidly progressive neurodegenerative disease. However, the molecular mechanism(s) leading from ganglioside accumulation to neurodegeneration is not known. We now examine the effect of ganglioside GM2 accumulation in a mouse model of Sandhoff disease (one of the GM2 gangliosidoses), the Hexb-/- mouse. Microsomes from Hexb-/- mouse brain showed a significant reduction in the rate of Ca2+-uptake via the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), which was prevented by feeding Hexb-/- mice with N-butyldeoxynojirimycin (NB-DNJ), an inhibitor of glycolipid synthesis that reduces GM2 storage. Changes in SERCA activity were not due to transcriptional regulation but rather because of a decrease in Vmax. Moreover, exogenously added GM2 had a similar effect on SERCA activity. The functional significance of these findings was established by the enhanced sensitivity of neurons cultured from embryonic Hexb-/- mice to cell death induced by thapsigargin, a specific SERCA i...Continue Reading

References

Jan 29, 1986·Biochemical and Biophysical Research Communications·C M Deber, L C Hsu
Mar 28, 1998·The Journal of Biological Chemistry·K M Wells, R F Abercrombie
Jun 5, 1998·Trends in Pharmacological Sciences·M TreimanS B Christensen
Sep 5, 1998·Journal of Inherited Metabolic Disease·T Kolter, K Sandhoff
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·M JeyakumarF M Platt
Nov 26, 1999·Biochimica Et Biophysica Acta·D J Mahuran
Feb 5, 2000·Mammalian Genome : Official Journal of the International Mammalian Genome Society·M Ver HeyenF Wuytack
Aug 22, 2000·European Journal of Biochemistry·D H MacLennan
Sep 27, 2000·Proceedings of the National Academy of Sciences of the United States of America·R WadaR L Proia
Sep 28, 2001·The Journal of Biological Chemistry·E BieberichR K Yu
Dec 26, 2001·Brain Research·Henry N NguyenDavid C Perry
May 23, 2002·Human Molecular Genetics·Rachel MyerowitzRichard L Proia
Jul 16, 2002·The Journal of Biological Chemistry·Carmen García-RuizJosé C Fernández-Checa
Aug 8, 2002·Neuron·Tony Wyss-Coray, Lennart Mucke
Aug 15, 2002·British Journal of Cancer·C RiebelingC C Geilen
Sep 12, 2002·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jacques BodennecAnthony H Futerman
Oct 9, 2002·Neuropathology and Applied Neurobiology·M JeyakumarF M Platt
Dec 4, 2002·Experimental Neurology·Christopher P TurnerScott A Rivkees
Dec 14, 2002·Basic Research in Cardiology·Konrad F FrankRobert H G Schwinger
Apr 24, 2003·The Journal of Biological Chemistry·Emyr Lloyd-EvansAnthony H Futerman

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Citations

Feb 13, 2007·Apoptosis : an International Journal on Programmed Cell Death·Albert MoralesJosé C Fernandez-Checa
Feb 18, 2010·Journal of Inherited Metabolic Disease·Raphael Schiffmann
Apr 30, 2010·Journal of Inherited Metabolic Disease·Cinzia Maria Bellettato, Maurizio Scarpa
May 12, 2010·Journal of Inherited Metabolic Disease·Danielle te VruchteDaniel John Sillence
Dec 2, 2004·Nature Reviews. Cancer·Yanjun Ma, Linda M Hendershot
Jul 3, 2004·Nature Reviews. Molecular Cell Biology·Anthony H Futerman, Gerrit van Meer
Jul 29, 2005·Nature Reviews. Neuroscience·Mylvaganam JeyakumarFrances M Platt
Jan 7, 2006·Cell Death and Differentiation·D LindholmL Korhonen
Jan 7, 2006·Cell Death and Differentiation·A d'AzzoR Sano
Jan 5, 2011·The Journal of Biological Chemistry·William C LamannaJeffrey D Esko
Mar 23, 2011·Human Molecular Genetics·Jacqueline A Hawkins-SalsburyMark S Sands
Mar 29, 2011·Cold Spring Harbor Perspectives in Biology·Djalila MekahliLudwig Missiaen
Apr 20, 2011·Cold Spring Harbor Perspectives in Biology·Heike Schulze, Konrad Sandhoff
Jul 9, 2011·Pharmacological Reviews·Grace E Stutzmann, Mark P Mattson
Mar 10, 2010·Journal of Lipid Research·You-Hai XuGregory A Grabowski
Sep 15, 2009·PloS One·Sang Ok Song, Jeffrey Varner
Aug 24, 2013·Drug Design, Development and Therapy·Shilpa A Patil, Gustavo H B Maegawa
Aug 24, 2010·Neuromolecular Medicine·Matthias Eckhardt
Dec 17, 2009·FEBS Letters·Elena Posse de Chaves, Simonetta Sipione
Oct 7, 2014·Experimental Neurology·Allison M BradburyDouglas R Martin
Jul 28, 2012·Progress in Lipid Research·Gerhild van Echten-Deckert, Jochen Walter
May 6, 2009·Progress in Neuro-psychopharmacology & Biological Psychiatry·Nachum Vaisman, Dori Pelled
Jan 15, 2005·Neurobiology of Disease·Dori PelledAnthony H Futerman
Feb 3, 2005·British Journal of Haematology·Ashok Vellodi
Nov 10, 2005·Journal of Neurochemistry·Luba Ginzburg, Anthony H Futerman
May 28, 2008·Acta Paediatrica. Supplement·Frances M Platt, Mylvaganam Jeyakumar
Oct 13, 2011·The Journal of Pathology·Timothy M Cox, M Begoña Cachón-González
Jan 19, 2010·Journal of Cellular Physiology·Vanessa Gonçalves PereiraVânia D'Almeida
Sep 3, 2004·Brain Research·Blanca C SalazarEsperanza Recio-Pinto
Sep 26, 2006·Biochimica Et Biophysica Acta·Anthony H Futerman
Dec 2, 2004·Brain Research. Brain Research Reviews·Laura Colombaioni, Mercedes Garcia-Gil
May 2, 2006·Biochemical and Biophysical Research Communications·Chunlei LiXujia Zhang
Oct 14, 2011·The Biochemical Journal·Anthony J MorganAntony Galione
Nov 3, 2010·The American Journal of Pathology·Sandrine VitryJean Michel Heard
May 31, 2015·Trends in Biochemical Sciences·Robert W Ledeen, Gusheng Wu
Jan 27, 2009·Molecular Genetics and Metabolism·Brigitte Rigat, Don Mahuran
Dec 30, 2008·Biochimica Et Biophysica Acta·Andrea Ballabio, Volkmar Gieselmann
Oct 1, 2008·Biochimica Et Biophysica Acta·Frances M Platt, Robin H Lachmann
Feb 1, 2015·Apoptosis : an International Journal on Programmed Cell Death·Carmen Garcia-RuizJosé C Fernández-Checa
Aug 16, 2016·Ageing Research Reviews·Emyr Lloyd-Evans, Luke J Haslett

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