β2 adrenergic receptor activation induces microglial NADPH oxidase activation and dopaminergic neurotoxicity through an ERK-dependent/protein kinase A-independent pathway

Li Qian, Xiaoming Hu, Dan Zhang, Amanda Snyder, Hung Ming Wu, Yachen Li, Belinda Wilson, Ru Band Lu, Jau Shyong Hong, Patrick M. Flood

研究成果: Article

27 引文 斯高帕斯(Scopus)

摘要

Activation of the β2 adrenergic receptor (β2AR) on immune cells has been reported to possess anti-inflammatory properties, however, the pro-inflammatory properties of β2AR activation remain unclear. In this study, using rat primary mesencephalic neuron-glia cultures, we report that salmeterol, a long-acting β2AR agonist, selectively induces dopaminergic (DA) neurotoxicity through its ability to activate microglia. Salmeterol selectively increased the production of reactive oxygen species (ROS) by NADPH oxidase (PHOX), the major superoxide-producing enzyme in microglia. A key role of PHOX in mediating salmeterol-induced neurotoxicity was demonstrated by the inhibition of DA neurotoxicity in cultures pretreated with diphenylene-iodonium (DPI), an inhibitor of PHOX activity. Mechanistic studies revealed the activation of microglia by salmeterol results in the selective phosphorylation of ERK, a signaling pathway required for the translocation of the PHOX cytosolic subunit p47phox to the cell membrane. Furthermore, we found ERK inhibition, but not protein kinase A (PKA) inhibition, significantly abolished salmeterol-induced superoxide production, p47phox translocation, and its ability to mediate neurotoxicity. Together, these findings indicate that β2AR activation induces microglial PHOX activation and DA neurotoxicity through an ERK-dependent/PKA-independent pathway.

原文English
頁(從 - 到)1600-1609
頁數10
期刊GLIA
57
發行號15
DOIs
出版狀態Published - 2009 十一月 15

All Science Journal Classification (ASJC) codes

  • Neurology
  • Cellular and Molecular Neuroscience

指紋 深入研究「β2 adrenergic receptor activation induces microglial NADPH oxidase activation and dopaminergic neurotoxicity through an ERK-dependent/protein kinase A-independent pathway」主題。共同形成了獨特的指紋。

  • 引用此

    Qian, L., Hu, X., Zhang, D., Snyder, A., Wu, H. M., Li, Y., Wilson, B., Lu, R. B., Hong, J. S., & Flood, P. M. (2009). β2 adrenergic receptor activation induces microglial NADPH oxidase activation and dopaminergic neurotoxicity through an ERK-dependent/protein kinase A-independent pathway. GLIA, 57(15), 1600-1609. https://doi.org/10.1002/glia.20873