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Molecular and Cellular Biology, May 2008, p. 3273-3280, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.02159-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Interleukin-1 Stimulates Glutamate Uptake in Glial Cells by Accelerating Membrane Trafficking of Na+/K+-ATPase via Actin Depolymerization{triangledown}

Kazuhiko Namekata,1 Chikako Harada,1 Kuniko Kohyama,2 Yoh Matsumoto,2 and Takayuki Harada1*

Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan,1 Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, Japan2

Received 5 December 2007/ Returned for modification 7 January 2008/ Accepted 29 February 2008

Interleukin-1 (IL-1) is a mediator of brain injury induced by ischemia, trauma, and chronic neurodegenerative disease. IL-1 also has a protective role by preventing neuronal cell death from glutamate neurotoxicity. However, the cellular mechanisms of IL-1 action remain unresolved. In the mammalian retina, glutamate/aspartate transporter (GLAST) is a Na+-dependent, major glutamate transporter localized to Müller glial cells, and loss of GLAST leads to glaucomatous retinal degeneration (T. Harada, C. Harada, K. Nakamura, H. A. Quah, A. Okumura, K. Namekata, T. Saeki, M. Aihara, H. Yoshida, A. Mitani, and K. Tanaka, J. Clin. Investig. 117:1763-1770, 2007). We show here that IL-1 increases glutamate uptake in Müller cells by a mechanism that involves increased membrane Na+/K+-ATPase localization, required for counteracting the Na+-glutamate cotransport. IL-1 activated the p38 mitogen-activated protein kinase (MAPK)/capase 11 pathway, which destabilizes the actin cytoskeleton allowing Na+/K+-ATPase membrane redistribution. Furthermore, pretreatment with IL-1 protected retinal neurons from glutamate neurotoxicity through p38 MAPK signaling. Our observations suggested that IL-1 acts as a potential neuroprotective agent by modulating the functions of the glia-neuron network.

* Corresponding author. Mailing address: Department of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu, Tokyo 183-8526, Japan. Phone: 81-42-325-3881. Fax: 81-42-321-8678. E-mail: harada{at}tmin.ac.jp

{triangledown} Published ahead of print on 10 March 2008.

Molecular and Cellular Biology, May 2008, p. 3273-3280, Vol. 28, No. 10
0270-7306/08/$08.00+0     doi:10.1128/MCB.02159-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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