NF-kappa B as a common signaling pathway in ganglioside-induced autophagic cell death and activation of astrocytes

作者：Hwang Jaegyu; Lee Ho Jae; Lee Won Ha; Suk Kyoungho^*

来源：Journal of Neuroimmunology, 2010, 226(1-2): 66-72.

DOI：10.1016/j.jneuroim.2010.05.037

• Ganglioside
• NE-kappa B
• Autophagy
• Astrocytes
• Rho
• Neuroinflammation

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-kappa B 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-kappa B in autophagic cell death and nitric oxide (NO) production in astrocytes. Gangliosides induced iNOS/GFAP expression and NF-kappa B activation. IKK inhibitor SC-514 and NF-kappa B inhibitor PDTC reduced ganglioside-induced astrocyte activation and cell death. Moreover, inhibition of NF-kappa B 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-kappa B 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.

• 出版日期2010-9-14