title: NF-κB as a common signaling pathway in ganglioside-induced autophagic cell death and activation of astrocytes.
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.
authors.affiliation: Department of Pharmacology, Brain Science and Engineering Institute, CMRI, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jaegyu
authors.initials: J
authors.lastname: Hwang
authors.forename: Ho-Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Won-Ha
authors.initials: WH
authors.lastname: Lee
authors.forename: Kyoungho
authors.initials: K
authors.lastname: Suk
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects* / Q000502:physiology*; D001921:Brain / Q000166:cytology; D002103:Cadaverine / Q000031:analogs & derivatives / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection / Q000379:methods; D019323:omega-N-Methylarginine / Q000494:pharmacology; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D005732:Gangliosides; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009479:Neuropeptides; D009573:Nitrites; D011725:Pyridines; C484602:Rac1 protein, mouse; C108830:Y 27632; D049452:Green Fluorescent Proteins; D019323:omega-N-Methylarginine; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; C008542:monodansylcadaverine; D002103:Cadaverine