Department of Neurology, Fujita Health University School of Medicine, Aichi, Japan.
Department of Neurology, Fujita Health University School of Medicine, Aichi, Japan.
Mol Cell Neurosci. 2018 Jun;89:42-48. doi: 10.1016/j.mcn.2018.03.012. Epub 2018 Mar 27.
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.
先前的研究表明，吉兰-巴雷综合征患者表达针对神经节苷脂 GM1（GM1）的自身抗体，尽管其对疾病发展的致病意义仍有待阐明。nSMase2 是神经元细胞中最具特征性的中性鞘磷脂酶（nSMase）。该酶的激活导致神经酰胺的产生，这是神经元细胞中细胞死亡程序的已知第二信使。我们通过测定其对 nSMase2 活性的影响，探讨了抗 GM1 抗体对稳定转染人 trk cDNA 的 PC12 细胞（PCtrk 细胞）鞘磷脂代谢的影响。我们在这里提供的数据强烈表明，抗 GM1 导致 PCtrk 细胞质膜鞘磷脂含量发生显著变化。抗 GM1 处理 PCtrk 细胞后，nSMase2 活性和 nSMase2 蛋白水平均显著降低，而酸性 SMase 活性保持不变。我们的结果首次表明，抗 GM1 可能对神经元细胞膜的脂代谢产生深远影响。
