| GM1 inhibits amyloid beta-protein-induced cytokine release. | |
| | |
MedLine Citation:
|
PMID: 9972868 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The ganglioside GM1 is known to play a pivotal role in neuronal survival and/or regeneration. Recently it has been shown that GM1 binds tightly with membrane-bound amyloid beta protein (A beta) and prevents its conversion from a helical to a beta-sheet structure. To examine the potential physiological consequences of this binding, we studied the effect of GM1 on A beta-stimulated release of proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and TNF-alpha, using the human monocytic cell line, THP-1, as a model system. Treatment of THP-1 cells with A beta 1-40 or A beta 25-35 resulted in an increased cytokine release from these cells. However, treatment of A beta-activated THP-1 cells with GM1 and several other complex gangliosides, but not hematosides and neutral glycosphingolipids such as asialo-GM1 (GA1), lactosylceramide, and globoside, significantly decreased the cytokine release. In contrast, this effect was not observed for lipopolysaccharide (LPS)-activated and thrombin-activated THP-1 cells, indicating that the ganglioside effect is specific for A beta-induced cytokine release. A direct interaction between GM1 and A beta was demonstrated using the surface plasmon resonance technique. We found that GM1 ganglioside exhibited higher affinity for A beta 1-40 than GA1, suggesting that the sialic acid moiety of GM1 is necessary for its interaction with A beta. We conclude that the inhibitory effect of GM1 on A beta-induced cytokine release may reflect pre-existing abnormalities in membrane transport at the stage of amyloid formation and that GM1 may induce conformational changes in A beta, resulting in diminished fibrillogenesis and prevention of the inflammatory response of neuronal cells in Alzheimer's disease. |
| | |
Authors:
|
T Ariga; R K Yu |
Related Documents
:
|
6270178 - Corticotropin/beta-lipotropin biosynthesis, processing, and release in nelson's syndrome. 17020298 - Direct electrophilic alpha-fluorination of imines: efficient synthesis of mono- and dif... 11263568 - Separation of monomethyl-benz[a]anthracene isomers using cyclodextrin-modified electrok... 11171998 - Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adul... 15094168 - Hepatic cellular immune responses in mice with "cure" and "non-cure" phenotype to leish... 22960458 - Behavioral effects of chronic methamphetamine treatment in hiv-1 gp120 transgenic mice. |
Publication Detail:
|
Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Neurochemical research Volume: 24 ISSN: 0364-3190 ISO Abbreviation: Neurochem. Res. Publication Date: 1999 Feb |
Date Detail:
|
Created Date: 1999-03-30 Completed Date: 1999-03-30 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 7613461 Medline TA: Neurochem Res Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 219-26 Citation Subset: IM |
Affiliation:
|
Eisai Co., Ltd., Tokyo, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amyloid beta-Protein
/
physiology* Cell Line G(M1) Ganglioside / physiology* Humans Interleukin-1 / metabolism* Interleukin-6 / metabolism* Monocytes / metabolism Tumor Necrosis Factor-alpha / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
NS11853-24/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amyloid beta-Protein; 0/Interleukin-1; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 37758-47-7/G(M1) Ganglioside |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cell reactions following acute brain injury: a review.
Next Document: Prolongation of life in an experimental model of aging in Drosophila melanogaster.