Interaction Among Mitochondria, Mitogen-Activated Protein Kinases, and Nuclear Factor-κB in Cellular Models of Parkinson's Disease
| Autor: | Halvorsen Em, David S. Cassarino, Parker William Davis, Sturgill Tw, James P. Bennett, Russell H. Swerdlow, Abramova Nn |
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| Rok vydání: | 2002 |
| Předmět: |
MAPK/ERK pathway
1-Methyl-4-phenylpyridinium MAP Kinase Kinase Kinase 1 Protein Serine-Threonine Kinases Mitochondrion Biochemistry Cytoplasmic hybrid Electron Transport Neuroblastoma Cellular and Molecular Neuroscience Pramipexole Tumor Cells Cultured Humans Benzothiazoles Protein kinase A Neurons biology MAP kinase kinase kinase Adenine Nucleotides Herbicides Superoxide Dismutase Kinase Adenine nucleotide translocator JNK Mitogen-Activated Protein Kinases NF-kappa B Parkinson Disease Free Radical Scavengers Mitochondria Cell biology Enzyme Activation Proto-Oncogene Proteins c-raf Oxidative Stress Thiazoles Mitogen-activated protein kinase biology.protein Mitogen-Activated Protein Kinases Peptides Signal Transduction |
| Zdroj: | Journal of Neurochemistry. 74:1384-1392 |
| ISSN: | 0022-3042 |
| Popis: | Oxidative stress induced by acute complex I inhibition with 1-methyl-4-phenylpyridinium ion activated biphasically the stress-activated c-Jun N-terminal kinase (JNK) and the early transcription factor nuclear factor-kappaB (NF-kappaB) in SH-SY5Y neuroblastoma cells. Early JNK activation was dependent on mitochondrial adenine nucleotide translocator (ANT) activity, whereas late-phase JNK activation and the cleavage of signaling proteins Raf-1 and mitogen-activated protein kinase (MAPK) kinase (MEK) kinase (MEKK)-1 appeared to be ANT-independent. Early NF-kappaB activation depended on MEK, later activation required an intact electron transport chain (ETC), and Parkinson's disease (PD) cybrid (mitochondrial transgenic cytoplasmic hybrid) cells had increased basal NF-kappaB activation. Mitochondria appear capable of signaling ETC impairment through MAPK modules and inducing protective NF-kappaB responses, which are increased by PD mitochondrial genes amplified in cybrid cells. Irreversible commitment to apoptosis in this cell model may derive from loss of Raf-1 and cleavage/activation of MEKK-1, processes reported in other models to be caspase-mediated. Therapeutic strategies that reduce mitochondrial activation of proapoptotic MAPK modules, i.e., JNK, and enhance survival pathways, i.e., NF-kappaB, may offer neuroprotection in this debilitating disease. |
| Databáze: | OpenAIRE |
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