Article ID Journal Published Year Pages File Type
3064656 Journal of Neuroimmunology 2010 7 Pages PDF
Abstract

We have previously shown that gangliosides induce autophagic cell death of brain astrocytes. As gangliosides are also known to induce inflammatory activation of astrocytes, we hypothesized that a canonical inflammatory signaling pathway NF-κB might be involved in the ganglioside-induced astrocyte cell death and activation. Using cultured mouse astrocytes and C6 rat glioma cell line, we determined the role of NF-κB in autophagic cell death and nitric oxide (NO) production in astrocytes. Gangliosides induced iNOS/GFAP expression and NF-κB activation. IKK inhibitor SC-514 and NF-κB inhibitor PDTC reduced ganglioside-induced astrocyte activation and cell death. Moreover, inhibition of NF-κB pathway also attenuated autophagy of astrocytes. Rho subfamily of small G proteins antagonized the ganglioside-induced astrocyte cell death as well as activation pathways. Taken together, IKK/NF-κB may constitute one of the common signaling pathways in ganglioside-induced astrocyte activation and autophagic cell death, and may play an important role in the ganglioside intracellular signaling that regulates astrocyte physiology and pathology.

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