Lipid content of brain, brain membrane lipid domains, and neurons from acid sphingomyelinase deficient mice.
The cholesterol, sphingolipid, and glycerophospholipid content of total brain, of detergent-resistant membranes prepared from the total brain, and of cerebellar granule cells differentiated in culture from wild type (WT) and acid sphingomyelinase knockout (ASMKO) were studied. Brains derived from 7-month-old ASMKO animals showed a fivefold higher level of sphingomyelin and a significant increase in ganglioside content, mainly because of monosialogangliosides GM3 and GM2 accumulation, while the cholesterol and glycerophospholipid content was unchanged with respect to WT animals. An increase in sphingomyelin, but not in gangliosides, was also detected in cultured cerebellar granule neurons from ASMKO mice, indicating that ganglioside accumulation is not a direct consequence of the enzyme defect. When a detergent-resistant membrane fraction was prepared from ASMKO brains, we observed that a higher detergent-to-protein ratio was needed than in WT animals. This likely reflects a reduced fluidity in restricted membrane areas because of a higher enrichment in sphingolipids in the case of ASMKO brain.
Scandroglio
Federica
F
Center of Excellence on Neurodegenerative Diseases, Department of Medical Chemistry, Biochemistry and Biotechnology, University of Milan, Segrate, Italy.
Venkata
Jagadish Kummetha
JK
Loberto
Nicoletta
N
Prioni
Simona
S
Schuchman
Edward H
EH
Chigorno
Vanna
V
Prinetti
Alessandro
A
Sonnino
Sandro
S
D020816:Amino Acid Motifs / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003902:Detergents / Q000494:pharmacology; D005732:Gangliosides / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics*; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000172:deficiency*; D013110:Sphingosine / Q000378:metabolism; D014316:Tritium / Q000378:metabolism
D003902:Detergents; D005732:Gangliosides; D008563:Membrane Lipids; D014316:Tritium; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine