title: Taxol protects against calcium-mediated death of differentiated rat pheochromocytoma cells.
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 microM) variably reduced cell survival to between 10 and 55% at 4h. However, when taxol 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.
authors.affiliation: Department of Neurology, Saint Louis University School of Medicine, Missouri.
authors.forename: W J
authors.initials: WJ
authors.lastname: Burke
authors.forename: G
authors.initials: G
authors.lastname: Raghu
authors.forename: R
authors.initials: R
authors.lastname: Strong
mesh_terms: D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats
chemical_list: D000001:Calcimycin; D017239:Paclitaxel; D002118:Calcium