Salsolinol, an Endogenous Neurotoxin, Activates JNK and NF-κB Signaling Pathways in Human Neuroblastoma Cells
| Autor: | Shaik Shavali, Piyarat Govitrapong, Manuchair Ebadi, Sawitri Wanpen, Patcharee Kooncumchoo |
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| Rok vydání: | 2007 |
| Předmět: |
Mitochondrion
Biology medicine.disease_cause Biochemistry Neuroblastoma Cellular and Molecular Neuroscience chemistry.chemical_compound Cell Line Tumor medicine Humans Neurotoxin Phosphorylation Electron Transport Complex I c-jun Dopaminergic JNK Mitogen-Activated Protein Kinases NF-kappa B Cytochromes c NF-κB General Medicine Isoquinolines Molecular biology Mitochondria Cell biology IκBα chemistry Signal transduction Reactive Oxygen Species Oxidative stress Signal Transduction |
| Zdroj: | Neurochemical Research. 32:443-450 |
| ISSN: | 1573-6903 0364-3190 |
| DOI: | 10.1007/s11064-006-9246-0 |
| Popis: | Salsolinol, an endogenous neurotoxin, is known to be involved in the pathogenesis of Parkinson's disease (PD). In the present study, we have investigated the effects of salsolinol on the activation of two different signaling pathways that involve c-Jun N-terminal kinase (JNK), and nuclear factor-kappaB, (NF-kappaB) in human dopaminergic neuroblastoma SH-SY5Y cells. Salsolinol treatment caused upregulation in the levels of c-Jun and phosphorylated c-Jun. It also caused degradation of IkappaBalpha and translocated the active NF-kappaB into the nucleus. The binding activity of NF-kappaB to DNA was enhanced by salsolinol in a concentration dependent manner. Furthermore, salsolinol decreased the levels of the anti-apoptotic protein Bcl-2, and increased pro-apoptotic protein Bax, while enhancing the release of cytochrome-c from mitochondria. Mitochondrial complex-I activity was significantly decreased and reactive oxygen species (ROS) were increased in salsolinol treated cells. These results partly suggest that salsolinol-induced JNK and NF-kappaB signaling pathways may be involved in induction of apoptosis in human dopaminergic neurons, as seen in Parkinson's disease. |
| Databáze: | OpenAIRE |
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