A Common Carcinogen Benzo[a]pyrene Causes Neuronal Death in Mouse via Microglial Activation
| Autor: | Debapriya Ghosh, Kallol Dutta, Kanhaiya Lal Kumawat, Anirban Basu, Arshed Nazmi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Programmed cell death
Public Health and Epidemiology/Environmental Health lcsh:Medicine Pharmacology Biology Nitric Oxide Proinflammatory cytokine Cell Line chemistry.chemical_compound Mice Neuroblastoma medicine Benzo(a)pyrene Animals lcsh:Science Carcinogen Cells Cultured Public Health and Epidemiology/Occupational and Industrial Medicine Neurons Multidisciplinary Microglia Cell Death Neuroscience/Neuronal and Glial Cell Biology lcsh:R Neurotoxicity Public Health and Epidemiology/Global Health medicine.disease Astrogliosis Nitric oxide synthase medicine.anatomical_structure chemistry Immunology biology.protein Carcinogens Cytokines lcsh:Q Environmental Pollutants Inflammation Mediators Neuroscience/Neurobiology of Disease and Regeneration Reactive Oxygen Species Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 5, Iss 4, p e9984 (2010) |
| ISSN: | 1932-6203 |
| Popis: | Background Benzo[a]pyrene (B[a]P) belongs to a class of polycyclic aromatic hydrocarbons that serve as micropollutants in the environment. B[a]P has been reported as a probable carcinogen in humans. Exposure to B[a]P can take place by ingestion of contaminated (especially grilled, roasted or smoked) food or water, or inhalation of polluted air. There are reports available that also suggests neurotoxicity as a result of B[a]P exposure, but the exact mechanism of action is unknown. Methodology/Principal Findings Using neuroblastoma cell line and primary cortical neuron culture, we demonstrated that B[a]P has no direct neurotoxic effect. We utilized both in vivo and in vitro systems to demonstrate that B[a]P causes microglial activation. Using microglial cell line and primary microglial culture, we showed for the first time that B[a]P administration results in elevation of reactive oxygen species within the microglia thereby causing depression of antioxidant protein levels; enhanced expression of inducible nitric oxide synthase, that results in increased production of NO from the cells. Synthesis and secretion of proinflammatory cytokines were also elevated within the microglia, possibly via the p38MAP kinase pathway. All these factors contributed to bystander death of neurons, in vitro. When administered to animals, B[a]P was found to cause microglial activation and astrogliosis in the brain with subsequent increase in proinflammatory cytokine levels. Conclusions/Significance Contrary to earlier published reports we found that B[a]P has no direct neurotoxic activity. However, it kills neurons in a bystander mechanism by activating the immune cells of the brain viz the microglia. For the first time, we have provided conclusive evidence regarding the mechanism by which the micropollutant B[a]P may actually cause damage to the central nervous system. In today's perspective, where rising pollution levels globally are a matter of grave concern, our study throws light on other health hazards that such pollutants may exert. |
| Databáze: | OpenAIRE |
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