Phytoalexin protects dopaminergic neurons against neurotoxicity by modulating myeloperoxidase levels in glial cells (P4199)

Autor: Chi Young Chang, Hee Jung Yoon, Eun Jung Park
Rok vydání: 2013
Předmět:
Zdroj: The Journal of Immunology. 190:112.33-112.33
ISSN: 1550-6606
0022-1767
Popis: Myeloperoxidase functions as a key molecular component of the host defense system against diverse pathogens. We have previously reported that increased myeloperoxidase levels and activity is a distinguishing feature of rotenone-exposed glial cells, and that either overactivation or deficiency of myeloperoxidase leads to pathological conditions in the brain. Here, we provide that modulation of myeloperoxidase levels in glia by resveratrol confers protective effects on rotenone-induced neurotoxicity. We show that resveratrol significantly reduced myeloperoxidase levels but did not trigger abnormal nitric oxide production in microglia and astrocytes. Resveratrol-induced down-regulation of myeloperoxidase markedly attenuated rotenone-triggered inflammatory responses including phagocytic activity and reactive oxygen species production in primary microglia and astrocytes. In addition, impaired responses of primary mixed glia from MPO knockout mice to rotenone were relieved by treatment with resveratrol. We further show that rotenone-induced neuronal injury, particularly dopaminergic cell death, was attenuated by resveratrol in neuron-glia co-cultures, but not in neurons cultured alone. Collectively, our findings provide that resveratrol influences glial responses to rotenone by regulating both myeloperoxidase and nitric oxide, and thus protects against rotenone-induced neuronal injury.
Databáze: OpenAIRE