2014年2月
TRPM2 contributes to LPS/IFN gamma-induced production of nitric oxide via the p38/JNK pathway in microglia
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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- 巻
- 444
- 号
- 2
- 開始ページ
- 212
- 終了ページ
- 217
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bbrc.2014.01.022
- 出版者・発行元
- ACADEMIC PRESS INC ELSEVIER SCIENCE
Microglia are immune cells that maintain brain homeostasis at a resting state by surveying the environment and engulfing debris. However, in some pathological conditions, microglia can produce neurotoxic factors such as pro-inflammatory cytokines and nitric oxide (NO) that lead to neuronal degeneration. Inflammation-induced calcium (Ca2+) signaling is thought to underlie this abnormal activation of microglia, but the mechanisms are still obscure. We previously showed that combined application of lipopolysaccharide and interferon gamma (LPS/IFN gamma) induced-production of NO in microglia from wild-type (WT) mice is significantly reduced in microglia from transient receptor potential melastatin 2 (TRPM2)-knockout (KO) mice. Here, we found that LPS/IFN gamma produced a late-onset Ca2+ signaling in WT microglia, which was abolished by application of the NADPH oxidase inhibitor diphenylene iodonium (DPI) and ML-171. In addition, pharmacological blockade or gene deletion of TRPM2 channel in microglia did not show this Ca2+ signaling. Furthermore, pharmacological manipulation and Western blotting revealed that Ca2+ mobilization, the proline-rich tyrosine kinase 2 (Pyk2), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun NH2-terminal kinase (JNK) contributed to TRPM2-mediated LPS/IFN gamma-induced activation, while the extracellular signal-regulated protein kinase (ERK) did not. These results suggest that LPS/IFN gamma activates TRPM2-mediated Ca2+ signaling, which in turn increases downstream p38 MAPK and JNK signaling and results in increased NO production in microglia. (C) 2014 Elsevier Inc. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bbrc.2014.01.022
- ISSN : 0006-291X
- eISSN : 1090-2104
- Web of Science ID : WOS:000331923500018