Taxol protects against calcium-mediated death of differentiated rat pheochromocytoma cells |
| |
| Institution: | 1. From the Departments of Neurology, Medicine and Anatomy, Saint Louis University School of Medicine and Veterans Administration Medical Center, St. Louis, Missouri, USA;2. Department of Cellular and Structural Biology University of Texas Health Science Center, San Antonio, USA;3. Department of Cellular and Pharmacology, University of Texas Health Science Center, San Antonio, USA;4. Geriatric Research, Education and Clinical Center, Audie L. Murphy Memorial Veterans Hospital, San Antonio, Texas, USA;1. College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China;2. Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China;1. Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, PA 16802, USA;2. Molecular Biology of Selenium Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA;1. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA;2. Brown Center for the Study of Children at Risk, Women and Infants Hospital, Warren Alpert School of Medicine of Brown University, Providence, RI, USA;3. Department of Biological Sciences, Dartmouth College, Hanover, NH, USA;4. Department of Earth Sciences, Dartmouth College, Hanover, NH, USA;5. Department of Genetics and Genome Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;6. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA;7. Department of Epidemiology, Geisel School of Medicine, Dartmouth College, Lebanon, NH, USA;8. Children’s Environmental Health and Disease Prevention Research Center at Dartmouth, Dartmouth College, Lebanon, NH, USA |
| |
| Abstract: | Elevated levels of intraneuronal calcium may contribute to neuronal death in both Alzheimer's disease and stroke. In part, this neuronal death may be due to calcium-induced disruption of microtubules and inhibition of axonal transport. Taxol stabilizes microtubules to disaggregation. To determine whether taxol could protect against calcium-mediated neuron cell death, a test system was established using a nerve growth factor-differentiated rat pheochromocytoma cell line (PC12 cells). PC12 cells were cultured with nerve growth factor to induce a neuronal phenotype. After 15 days, the cells were exposed to taxol, the calcium ionophore, A23187, or taxol plus ionophore for up to 24 h. Taxol alone reduced cell survival in a concentration dependent manner. At a concentration of 50 nM survival was reduced to between 63% and 84% of control after 4 h of exposure. The ionophore (1 μM) variably reduced cell survival to between 10 and 55% at 4h. However, when tacol was added to the ionophore the cell survival was significantly increased by 1.5 to 4-fold. The protective effect of taxol lasted up to 24h. We conclude that taxol has a protective effect on calcium-mediated neurotoxicity. Drugs targeting underlying cellular mechanisms involved in calcium-mediated neuronal death may lead to successful therapy for Alzheimer's disease and stroke. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
