Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4347946 | Neuroscience Letters | 2008 | 6 Pages |
Abstract
Hypoxia induces an inflammatory activation of microglia during cerebral ischemia. The transcription factor of hypoxia-inducible genes hypoxia-inducible factor-1 (HIF-1) is known to be involved in inflammation and immune response. Although baicalein (BE), a flavonoid, is shown to have anti-inflammatory effects and attenuate ischemic injury, its action mechanism is not understood well. Thus, we examined effect of BE on hypoxia-induced HIF-1 activation and its signaling mechanism in BV2 microglial cells. BE inhibited hypoxia-induced HIF-1α protein accumulation and HIF-1 transcriptional activation. Consistently, BE suppressed hypoxia-induced expression of hypoxia responsive genes, iNOS, COX-2, and VEGF. We then showed that BE inhibited hypoxia-induced phosphorylation of Akt but not that of ERK and p38. Moreover, BE inhibited hypoxia-induced PI 3-kinase activation. Finally, we showed that BE inhibited hypoxia-induced ROS generation, and an antioxidant N-acetylcysteine reduced hypoxia-induced HIF-1α and iNOS protein expression and PI 3-kinase/Akt activation in BV2 microglia. Taken together, these results suggest that BE suppresses hypoxia-induced HIF-1α protein and activation as well as expression of hypoxia responsive genes by inhibiting ROS and PI 3-kinase/Akt pathway in BV2 microglia.
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Authors
Keun Young Hwang, Young Taek Oh, Hana Yoon, Jinhwa Lee, Hocheol Kim, Wonchae Choe, Insug Kang,