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Originally published In Press as doi:10.1074/jbc.M707330200 on October 31, 2007
J. Biol. Chem., Vol. 283, Issue 2, 693-699, January 11, 2008
Tumor Necrosis Factor Enhances Nicotinic Receptor Up-regulation via a p38MAPK-dependent Pathway*
Lorise C. Gahring 1,
Amber V. Osborne-Hereford¶2,
Gustavo A. Vasquez-Opazo , and
Scott W. Rogers ||
From the
Salt Lake City Veterans Affairs-Geriatrics Research, Education, and Clinical Center, Salt Lake City, Utah 84148 and the Departments of Internal Medicine, ¶Pathology, and ||Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132
A response by key neuronal nicotinic acetylcholine receptors (nAChRs) to sustained nicotine exposure is up-regulation. Although this unusual receptor characteristic contributes to processes ranging from aging to addiction, the normal physiologic reason for this response is unknown. We find that up-regulation of [3H]epibatidine binding and function in HEK293 cells stably expressing 4β2-nAChR is significantly enhanced by co-application of the proinflammatory cytokine, tumor necrosis factor . The mechanism of tumor necrosis factor -enhanced up-regulation requires transcription, new protein synthesis, and signaling through p38MAPK as demonstrated by complete inhibition using SB 202190. This finding extends the possibilities for nAChR-inflammatory interactions in normal physiological processes and offers novel insights into endogenous mechanisms that can modify up-regulation.
Received for publication, August 31, 2007
, and in revised form, October 29, 2007.
* This work was supported by NIDA/NHBLI, National Institutes of Health, Grants PO1 HL72903, DA015148, and AG17517 and Veterans Affairs-Merit funding (to L. C. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
2 Supported by the Browning Foundation of Utah.
1 To whom correspondence should be addressed: University of Utah School of Medicine 2C132, 30 North 1900 East, Salt Lake City, UT 84132. Fax: 801-585-3884; E-mail: Lorise.Gahring{at}hsc.utah.edu.

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Copyright © 2008 by the American Society for Biochemistry and Molecular Biology.
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