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Gangliosides induce autophagic cell death in astrocytes

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Affiliated Author(s)
권택규
Alternative Author(s)
Kwon, Taeg Kyu
Journal Title
British Journal of Pharmacology
ISSN
0007-1188
Issued Date
2010
Abstract
Keywords:

ganglioside;
autophagy;
astrocytes;
reactive oxygen species;
mTOR



Background and purpose:  Gangliosides, sialic acid-containing glycosphingolipids, abundant in brain, are involved in neuronal function and disease, but the precise molecular mechanisms underlying their physiological or pathological activities are poorly understood. In this study, the pathological role of gangliosides in the extracellular milieu with respect to glial cell death and lipid raft/membrane disruption was investigated.


Experimental approach:  We determined the effect of gangliosides on astrocyte death or survival using primary astrocyte cultures and astrocytoma/glioma cell lines as a model. Signalling pathways of ganglioside-induced autophagic cell death of astrocytes were examined using pharmacological inhibitors and biochemical and genetic assays.


Key results:  Gangliosides induced autophagic cell death in based on the following observations. Incubation of the cells with a mixture of gangliosides increased a punctate distribution of fluorescently labelled microtubule-associated protein 1 light chain 3 (GFP-LC3), the ratio of LC3-II/LC3-I and LC3 flux. Gangliosides also increased the formation of autophagic vacuoles as revealed by monodansylcadaverine staining. Ganglioside-induced cell death was inhibited by either a knockdown of beclin-1/Atg-6 or Atg-7 gene expression or by 3-methyladenine, an inhibitor of autophagy. Reactive oxygen species (ROS) were involved in ganglioside-induced autophagic cell death of astrocytes, because gangliosides induced ROS production and ROS scavengers decreased autophagic cell death. In addition, lipid rafts played an important role in ganglioside-induced astrocyte death.


Conclusions and implications:  Gangliosides released under pathological conditions may induce autophagic cell death of astrocytes, identifying a neuropathological role for gangliosides.
Department
Dept. of Immunology (면역학)
Publisher
School of Medicine
Citation
Jaegyu Hwang et al. (2010). Gangliosides induce autophagic cell death in astrocytes. British Journal of Pharmacology, 159(3), 586–603. doi: 10.1111/j.1476-5381.2009.00563.x
Type
Article
ISSN
0007-1188
DOI
10.1111/j.1476-5381.2009.00563.x
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35266
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Immunology (면역학)
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