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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Sai, Yan Chen, Junfeng Wu, Qiang Liu, Hiu Zhao, Jiqing Dong, Zhaojun |
| Description | Author Affiliation: Sai Y ( Department of Toxicology, School of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, PR China.) |
| Abstract | Rotenone, a mitochondrial complex-I inhibitor, has been verified to cause dopaminergic neurons degeneration in vivo and in vitro, and the substantia nigra pars compacta (SNc) and the striatum are the main target organs of rotenone in the rat brain. However, whether rotenone could cause damage to other regions in the brain has been unclear till now. To address this question, the rotenone-induced neurotoxicity in the hippocampal neurons was investigated in the present study. Rotenone (4mg/kg) was given to the male Sprague-Dawley rats per day for up to 4 weeks by using the osmotic minipumps. Results showed that neurodegeneration was formed and phosphorylated ERK1/2 (p-ERK1/2) was induced in the hippocampus of rats following rotenone treatment. In additionally, Ras, PKA and PKC were also activated and free [Ca(2+)](i) was increased in the cytoplasm of the hippocampus neurons. To determine how ERK cascade was activated, studies in the primary cultured hippocampus neurons were carried out in a further. Cell viability was reduced, and also apoptosis was induced in vitro following rotenone administration. Expressions of p-ERK1/2 were also enhanced evidently in the cultured neurons treated by rotenone. Free [Ca(2+)](i) was also increased in the cultured neurons induced by rotenone. However, this influx might not take main effect in ERK1/2 phosphorylation. In conclusion, Ras-Raf-1-MEK-ERK1/2 classic signal pathway, not by PKA/PKC alternative pathway may be the mainly contributor to the ERK1/2 phosphorylation. And also, Ras protein is the dominant activator in the ERK phosphorylation induced by rotenone. |
| File Format | HTM / HTML |
| ISSN | 13826689 |
| Issue Number | 3 |
| Journal | Environmental Toxicology and Pharmacology |
| Volume Number | 27 |
| e-ISSN | 18727077 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2009-05-01 |
| Publisher Place | Netherlands |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Environmental Health Discipline Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Health, Toxicology and Mutagenesis Medicine Toxicology Pharmacology |
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