کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1933881 | 1050629 | 2009 | 5 صفحه PDF | دانلود رایگان |
Role of microglial Nrf2 activation in preventing neuronal death caused by microglial hyperactivation is investigated by using BV-2 microglial cells as modulator and primary neurons as target. Pretreatment of microglial cells with tBHQ, a phenolic antioxidant activating Nrf2, attenuated the LPS-derived overproduction of pro-inflammatory neurotoxic mediators like TNF-α, IL-1β, IL-6, PGE2, and NO as well as the morphological changes associated with microglial hyperactivation. Pretreatment of BV-2 cells with tBHQ suppressed LPS-induced phosphorylation of p38 required for overproduction of neurotoxic mediators. Results obtained using Nrf2-specific shRNA showed that expression of Nrf2 in microglia plays a critical role in tBHQ-derived suppression of LPS-induced p38 phosphorylation and microglial hyperactivation. Conditioned culture media taken from LPS-stimulated microglia cause neuronal death. However, the conditioned media taken from tBHQ-pretreated and LPS-stimulated microglia did not cause death of primary neurons. This suggested that prior activation of Nrf2 in microglia may inhibit microglial hyperactivation and prevent neuronal death.
Journal: Biochemical and Biophysical Research Communications - Volume 380, Issue 3, 13 March 2009, Pages 449–453