Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity

Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in...

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Bibliographic Details
Published in:	Molecular and cellular neuroscience Vol. 89; pp. 42 - 48
Main Authors:	Ueda, Akihiro, Shima, Sayuri, Murate, Kenitiroh, Kikuchi, Kouichi, Nagao, Ryunosuke, Maeda, Toshiki, Muto, Eri, Niimi, Yoshiki, Mizutani, Yasuaki, Mutoh, Tatsuro
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-06-2018
Subjects:	Animals Anti-GM1 antibody Antibodies - pharmacology Cell Membrane - drug effects Cell Membrane - metabolism Ceramide G(M1) Ganglioside - immunology Guillain-Barre Syndrome - metabolism Guillain-Barré syndrome (GBS) Humans Neutral sphingomyelinase PC12 Cells Rats Sphingomyelin Sphingomyelin Phosphodiesterase - metabolism Sphingomyelins - metabolism Sphingomyelin Ceramide Anti-GM1 antibody Neutral sphingomyelinase Guillain-Barré syndrome (GBS)
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Summary:	Previous studies have shown that patients with Guillain-Barré syndrome express autoantibodies against ganglioside GM1 (GM1), although its pathogenic significance for the development of the disease remains to be elucidated. nSMase2 is the best characterized neutral sphingomyelinase (nSMase) found in neuronal cells. Activation of this enzyme leads to ceramide production, which is a known second messenger of the cell-death program in neuronal cells. We have explored the effects of anti-GM1 antibodies on sphingomyelin metabolism of PC12 cells stably transfected with human trk cDNA (PCtrk cells) by determining their effects on nSMase2 activity. The data we present here strongly suggest that anti-GM1 caused a significant change in sphingomyelin content of the membrane fraction in PCtrk cells. Both nSMase2 activity and the level of nSMase2 protein were significantly decreased by anti-GM1 treatment of PCtrk cells, while acidic SMase activities remained unchanged. Our results indicate, for the first time, that anti-GM1 may produce profound impacts on lipid metabolism in neuronal cell membranes. •Anti-GM1 antibodies are often found in patients with Guillain-Barré syndrome.•Anti-GM1 antibodies inhibit membrane neutral sphingomyelinase activity.•It in turn caused significant change of membrane sphingomyelin contents.•It also inhibit exosome secretion into culture medium.•Thus, this study revealed new aspect of the autoantibody to neuronal cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1044-7431 1095-9327
DOI:	10.1016/j.mcn.2018.03.012