HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 43, 32164-32174, October 27, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/43/32164    most recent M602369200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Woo, C.-H. Articles by Abe, J.-i. Search for Related Content PubMed PubMed Citation Articles by Woo, C.-H. Articles by Abe, J.-i. Social Bookmarking                      What's this?

ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor (PPAR) Stimulation^*

From the Cardiovascular Research Institute, University of Rochester, Rochester, New York 14642

Peroxisome proliferator-activated receptors (PPAR) decrease the production of cytokine and inducible nitric-oxide synthase (iNOS) expression, which are associated with aging-related inflammation and insulin resistance. Recently, the involvement of the induction of heme oxygenase-1 (HO-1) in regulating inflammation has been suggested, but the exact mechanisms for reducing inflammation by HO-1 remains unclear. We found that overexpression of HO-1 and [Ru(CO)₃Cl₂]₂, a carbon monoxide (CO)-releasing compound, increased not only ERK5 kinase activity, but also its transcriptional activity measured by luciferase assay with the transfection of the Gal4-ERK5 reporter gene. This transcriptional activity is required for coactivation of PPAR by ERK5 in C2C12 cells. [Ru(CO)₃Cl₂]₂ activated PPAR transcriptional activity via the MEK5/ERK5 signaling pathway. The inhibition of NF-B activity by ERK5 activation was reversed by a dominant negative form of PPAR suggesting that ERK5/PPAR activation is required for the anti-inflammatory effects of CO and HO-1. Based on these data, we propose a new mechanism by which CO and HO-1 mediate anti-inflammatory effects via activating ERK5/PPAR, and ERK5 mediates CO and HO-1-induced PPAR activation via its interaction with PPAR.

Received for publication, March 14, 2006 , and in revised form, July 19, 2006.

^* This work was supported by American Heart Association Postdoctoral Fellowship 0325769T (to S. I.) and National Institutes of Health Grants GM071485-01A1 and HL-077789-01A1 (to J.-I. A. and C. Y.). 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.

¹ To whom correspondence should be addressed: Box 679, 601 Elmwood Ave., Rochester, NY 14642. Tel.: 585-273-1686; Fax: 585-273-1497; E-mail: jun-ichi_abe{at}urmc.rochester.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. H. V. Remels, R. C. J. Langen, H. R. Gosker, A. P. Russell, F. Spaapen, J. W. Voncken, P. Schrauwen, and A. M. W. J. Schols PPAR{gamma} inhibits NF-{kappa}B-dependent transcriptional activation in skeletal muscle Am J Physiol Endocrinol Metab, July 1, 2009; 297(1): E174 - E183. [Abstract] [Full Text] [PDF]

				M. Bilban, P. Haslinger, J. Prast, F. Klinglmuller, T. Woelfel, S. Haider, A. Sachs, L. E. Otterbein, G. Desoye, U. Hiden, et al. Identification of Novel Trophoblast Invasion-Related Genes: Heme Oxygenase-1 Controls Motility via Peroxisome Proliferator-Activated Receptor {gamma} Endocrinology, February 1, 2009; 150(2): 1000 - 1013. [Abstract] [Full Text] [PDF]

				W. Shan, P. S. Palkar, I. A. Murray, E. I. McDevitt, M. J. Kennett, B. H. Kang, H. C. Isom, G. H. Perdew, F. J. Gonzalez, and J. M. Peters Ligand Activation of Peroxisome Proliferator-Activated Receptor {beta}/{delta} (PPAR{beta}/{delta}) Attenuates Carbon Tetrachloride Hepatotoxicity by Downregulating Proinflammatory Gene Expression Toxicol. Sci., October 1, 2008; 105(2): 418 - 428. [Abstract] [Full Text] [PDF]

				A. H. Remels, H. R. Gosker, P. Schrauwen, R. C. Langen, and A. M. Schols Peroxisome proliferator-activated receptors: a therapeutic target in COPD? Eur. Respir. J., March 1, 2008; 31(3): 502 - 508. [Abstract] [Full Text] [PDF]

				H. E. Hollingshead, M. G. Borland, A. N. Billin, T. M. Willson, F. J. Gonzalez, and J. M. Peters Ligand activation of peroxisome proliferator-activated receptor-{beta}/{delta} (PPAR{beta}/{delta}) and inhibition of cyclooxygenase 2 (COX2) attenuate colon carcinogenesis through independent signaling mechanisms Carcinogenesis, January 1, 2008; 29(1): 169 - 176. [Abstract] [Full Text] [PDF]

				H. E. Hollingshead, R. L. Killins, M. G. Borland, E. E. Girroir, A. N. Billin, T. M. Willson, A. K. Sharma, S. Amin, F. J. Gonzalez, and J. M. Peters Peroxisome proliferator-activated receptor- /{delta} (PPAR /{delta}) ligands do not potentiate growth of human cancer cell lines Carcinogenesis, December 1, 2007; 28(12): 2641 - 2649. [Abstract] [Full Text] [PDF]