The Role of De Novo Catecholamine Synthesis in Mediating Methylmercury-Induced Vesicular Dopamine Release From Rat Pheochromocytoma (PC12) Cells
| Autor: | John L. Goudreau, Chelsea T. Tiernan, Keith J. Lookingland, William D. Atchison, Ethan A. Edwin |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Time Factors Cell Survival Dopamine Cell Culture Techniques Intracellular Space Vesicular Transport Proteins chemistry.chemical_element Calcium Toxicology PC12 Cells Exocytosis Internal medicine medicine Extracellular Animals Tyrosine Hydroxylase Inhibitor Dose-Response Relationship Drug Tyrosine hydroxylase Chemistry Membrane Transport Proteins Methylmercury Compounds Reserpine Rats Endocrinology Environmental Pollutants Extracellular Space Intracellular Research Article medicine.drug |
| Zdroj: | Toxicological Sciences. 133:125-132 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kft025 |
| Popis: | The purpose of this study was to characterize methylmercury (MeHg)–induced dopamine (DA) release from undifferentiated pheochromocytoma (PC12) cells and to examine the potential role for DA synthesis in this process. MeHg caused a significant increase in DA release that was both concentration- and time-dependent. DA release was significantly increased by 2µM MeHg at 60min and by 5µM MeHg at 30min; 1µM MeHg was without effect. Because DA release induced by 5µM MeHg was associated with a significant percentage of cell death at 60 and 120min, 2µM MeHg was chosen for further characterization of release mechanisms. MeHg-induced DA release was attenuated but not abolished in the absence of extracellular calcium, whereas the vesicular content depleting drug reserpine (50nM) abolished release. Thus, MeHg-induced DA release requires vesicular exocytosis but not extracellular calcium. MeHg also increased intracellular DA and the rate of DA storage utilization, suggesting a role for DA synthesis in MeHg-induced DA release. The tyrosine hydroxylase inhibitor α-methyltyrosine (300µM, 24h) completely abolished MeHg-induced DA release. MeHg significantly increased DA precursor accumulation in cells treated with 3-hydroxybenzylhydrazine (10µM), revealing that MeHg increases tyrosine hydroxylase activity. Overall, these data demonstrate that MeHg facilitates DA synthesis, increases intracellular DA, and augments vesicular exocytosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|