Document Detail


GD3 accumulation in cell surface lipid rafts prior to mitochondrial targeting contributes to amyloid-β-induced apoptosis.
MedLine Citation:
PMID:  20890432     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Neuronal apoptosis induced by amyloid β-peptide (Aβ) plays an important role in the pathophysiology of Alzheimer's disease (AD). However, the molecular mechanism underlying Aβ-induced apoptosis remains undetermined. The disialoganglioside GD3 involves ceramide-, Fas- and TNF-α-mediated apoptosis in lymphoid cells and hepatocytes. Although the implication of GD3 has been suggested, the precise role of GD3 in Aβ-induced apoptosis is still unclear. Here, we investigated the changes of GD3 metabolism and characterized the distribution and trafficking of GD3 during Aβ-induced apoptosis using human brain-derived TE671 cells. Extracellular Aβ-induced apoptosis in a mitochondrial-dependent manner. GD3 level was negligible in the basal condition. However, in response to extracellular Aβ, both the expression of GD3 synthase mRNA and the intracellular GD3 level were dramatically increased. Neosynthesized GD3 rapidly accumulated in cell surface lipid microdomains, and was then translocated to mitochondria to execute the apoptosis. Disruption of membrane lipid microdomains with methyl-β-cyclodextrin significantly prevented both GD3 accumulation in cell surface and Aβ-induced apoptosis. Our data suggest that rapidly accumulated GD3 in plasma membrane lipid microdomains prior to mitochondrial translocation is one of the key events in Aβ-induced apoptosis.
Authors:
Jong-Kook Kim; Sang-Ho Kim; Hee-Young Cho; Hee-Soo Shin; Hye-Ryen Sung; Jin-Ran Jung; Mei-Lian Quan; Dong-Hong Jiang; Hae-Rahn Bae
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-17
Journal Detail:
Title:  Journal of Korean medical science     Volume:  25     ISSN:  1598-6357     ISO Abbreviation:  J. Korean Med. Sci.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-04     Completed Date:  2011-02-17     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8703518     Medline TA:  J Korean Med Sci     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  1492-8     Citation Subset:  IM    
Affiliation:
Department of Neurology, Dong-A University College of Medicine, Medical Science Research Center, Busan, Korea.
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MeSH Terms
Descriptor/Qualifier:
Amyloid beta-Peptides / pharmacology*
Apoptosis*
Cell Line
Gangliosides / metabolism*,  physiology
Humans
Membrane Microdomains / metabolism*
Mitochondria / metabolism*
Sialyltransferases / genetics,  metabolism
beta-Cyclodextrins / pharmacology
Chemical
Reg. No./Substance:
0/Amyloid beta-Peptides; 0/Gangliosides; 0/beta-Cyclodextrins; 62010-37-1/ganglioside, GD3; EC 2.4.99.-/Sialyltransferases; EC 2.4.99.8/alpha-N-acetylneuraminate alpha-2,8-sialyltransferase; JV039JZZ3A/betadex
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