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

Akihiro Ueda, Sayuri Shima, Kenitiroh Murate, Kouichi Kikuchi, Ryunosuke Nagao, Toshiki Maeda, Eri Muto, Yoshiki Niimi, Yasuaki Mizutani, Tatsuro Mutoh

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)42-48
Number of pages7
JournalMolecular and Cellular Neuroscience
Volume89
DOIs
Publication statusPublished - 01-06-2018

Fingerprint

G(M1) Ganglioside
Sphingomyelin Phosphodiesterase
Sphingomyelins
Membranes
Antibodies
Enzyme Activation
Ceramides
PC12 Cells
Second Messenger Systems
Lipid Metabolism
Autoantibodies
Anti-Idiotypic Antibodies
Cell Death
Complementary DNA
Cell Membrane
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Ueda, Akihiro ; Shima, Sayuri ; Murate, Kenitiroh ; Kikuchi, Kouichi ; Nagao, Ryunosuke ; Maeda, Toshiki ; Muto, Eri ; Niimi, Yoshiki ; Mizutani, Yasuaki ; Mutoh, Tatsuro. / Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity. In: Molecular and Cellular Neuroscience. 2018 ; Vol. 89. pp. 42-48.
@article{e6beafd9074b44e2bd55067ed91fa901,
title = "Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity",
abstract = "Previous studies have shown that patients with Guillain-Barr{\'e} 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.",
author = "Akihiro Ueda and Sayuri Shima and Kenitiroh Murate and Kouichi Kikuchi and Ryunosuke Nagao and Toshiki Maeda and Eri Muto and Yoshiki Niimi and Yasuaki Mizutani and Tatsuro Mutoh",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.mcn.2018.03.012",
language = "English",
volume = "89",
pages = "42--48",
journal = "Molecular and Cellular Neurosciences",
issn = "1044-7431",
publisher = "Academic Press Inc.",

}

Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity. / Ueda, Akihiro; Shima, Sayuri; Murate, Kenitiroh; Kikuchi, Kouichi; Nagao, Ryunosuke; Maeda, Toshiki; Muto, Eri; Niimi, Yoshiki; Mizutani, Yasuaki; Mutoh, Tatsuro.

In: Molecular and Cellular Neuroscience, Vol. 89, 01.06.2018, p. 42-48.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-GM1 ganglioside antibodies modulate membrane-associated sphingomyelin metabolism by altering neutral sphingomyelinase activity

AU - Ueda, Akihiro

AU - Shima, Sayuri

AU - Murate, Kenitiroh

AU - Kikuchi, Kouichi

AU - Nagao, Ryunosuke

AU - Maeda, Toshiki

AU - Muto, Eri

AU - Niimi, Yoshiki

AU - Mizutani, Yasuaki

AU - Mutoh, Tatsuro

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85045049690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045049690&partnerID=8YFLogxK

U2 - 10.1016/j.mcn.2018.03.012

DO - 10.1016/j.mcn.2018.03.012

M3 - Article

AN - SCOPUS:85045049690

VL - 89

SP - 42

EP - 48

JO - Molecular and Cellular Neurosciences

JF - Molecular and Cellular Neurosciences

SN - 1044-7431

ER -