Interferon-γ directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-γ receptor and AMPA GluR1 receptor Tetsuya Mizuno * ,1 ,2 , Guiqin Zhang * ,1 , Hideyuki Takeuchi * , Jun Kawanokuchi * , Jinyan Wang * , Yoshifumi Sonobe * , Shijie Jin * , Naoki Takada † , Yukio Komatsu † and Akio Suzumura * * Department of Neuroimmunology and † Department of Visual Neuroscience, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan 2 Correspondence: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, 464-8601 Japan. E-mail: tmizuno@riem.nagoya-u.ac.jp Interferon-γ (IFN-γ) is a proinflammatory cytokine that plays a pivotal role in pathology of diseases in the central nervous system (CNS), such as multiple sclerosis. However, the direct effect of IFN-γ on neuronal cells has yet to be elucidated. We show here that IFN-γ directly induces neuronal dysfunction, which appears as dendritic bead formation in mouse cortical neurons and enhances glutamate neurotoxicity mediated via alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors but not N -methyl- D -aspartate receptors. In the CNS, IFN-γ receptor forms a unique, neuron-specific, calcium-permeable receptor complex with AMPA receptor subunit GluR1. Through this receptor complex, IFN-γ phosphorylates GluR1 at serine 845 position by JAK1·2/STAT1 pathway, increases Ca 2+ influx and following nitric oxide production, and subsequently decreases ATP production, leading to the dendritic bead formation. These findings provide novel mechanisms of neuronal excitotoxicity, which may occur in both inflammatory and neurodegenerative diseases in the CNS.—Mizuno, T., Zhang, G., Takeuchi, H., Kawanokuchi, J., Wang, J., Sonobe, Y., Jin, S., Takada, N., Komatsu, Y., Suzumura, A. Interferon-γ directly induces neurotoxicity through a neuron specific, calcium- permeable complex of IFN-γ receptor and AMPA GluR1 receptor. Key Words: proinflammatory cytokine • neuronal dysfunction
End of preview. The entire article is 10 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/interferon-directly-induces-neurotoxicity-through-a-neuron-specific-a20DN3yNWI
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Interferon-γ directly induces neurotoxicity through a neuron specific, calcium-permeable complex of IFN-γ receptor and AMPA GluR1 receptor
Mizuno, Tetsuya; Zhang, Guiqin; Takeuchi, Hideyuki; Kawanokuchi, Jun; Wang, Jinyan; Sonobe, Yoshifumi; Jin, Shijie; Takada, Naoki; Komatsu, Yukio; Suzumura, Akio
Follow The FASEB Journal
, Volume 22 (6): 1797
Fed of American Socs for Experimental Biology – Jun 1, 2008
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
