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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| Published in: | Molecular and cellular neuroscience Vol. 89; pp. 42 - 48 |
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| Main Authors: | , , , , , , , , , |
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01-06-2018
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| Abstract | 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. |
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| AbstractList | 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. 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. |
| Author | Ueda, Akihiro Murate, Kenitiroh Nagao, Ryunosuke Muto, Eri Mizutani, Yasuaki Mutoh, Tatsuro Maeda, Toshiki Shima, Sayuri Kikuchi, Kouichi Niimi, Yoshiki |
| Author_xml | – sequence: 1 givenname: Akihiro surname: Ueda fullname: Ueda, Akihiro – sequence: 2 givenname: Sayuri surname: Shima fullname: Shima, Sayuri – sequence: 3 givenname: Kenitiroh surname: Murate fullname: Murate, Kenitiroh – sequence: 4 givenname: Kouichi surname: Kikuchi fullname: Kikuchi, Kouichi – sequence: 5 givenname: Ryunosuke surname: Nagao fullname: Nagao, Ryunosuke – sequence: 6 givenname: Toshiki surname: Maeda fullname: Maeda, Toshiki – sequence: 7 givenname: Eri surname: Muto fullname: Muto, Eri – sequence: 8 givenname: Yoshiki surname: Niimi fullname: Niimi, Yoshiki – sequence: 9 givenname: Yasuaki surname: Mizutani fullname: Mizutani, Yasuaki – sequence: 10 givenname: Tatsuro orcidid: 0000-0001-7712-8481 surname: Mutoh fullname: Mutoh, Tatsuro email: tmutoh@fujita-hu.ac.jp |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29601870$$D View this record in MEDLINE/PubMed |
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| Keywords | Sphingomyelin Ceramide Anti-GM1 antibody Neutral sphingomyelinase Guillain-Barré syndrome (GBS) |
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| SubjectTerms | 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 |
| Title | Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity |
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