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

J. Biol. Chem., Vol. 281, Issue 11, 7244-7252, March 17, 2006

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 281/11/7244    most recent M510461200v1 Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nilsson, E. C. Articles by Mahlapuu, M. Search for Related Content PubMed PubMed Citation Articles by Nilsson, E. C. Articles by Mahlapuu, M. Social Bookmarking                      What's this?

Opposite Transcriptional Regulation in Skeletal Muscle of AMP-activated Protein Kinase 3 R225Q Transgenic Versus Knock-out Mice^*

Elisabeth C. Nilsson, Yun Chau Long, Sofia Martinsson, Stephan Glund, Pablo Garcia-Roves, L. Thomas Svensson, Leif Andersson^¶, Juleen R. Zierath, and Margit Mahlapuu¹

From the Arexis AB, Biotech Center, Arvid Wallgrens Backe 20, SE-413 46 Göteborg, the Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, and the ^¶Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 24 Uppsala, Sweden

AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory -subunit of the kinase, AMPK 3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK 3 mutant (R225Q) transgenic (TgPrkag3^225Q) and 3 knock-out (Prkag3^-/-) mice. We determined AMPK 3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from 3 mutant transgenic and knock-out mice using oligonucleotide microarray technology. Evidence is provided for coordinated and reciprocal regulation of multiple key components in glucose and fat metabolism, as well as skeletal muscle ergogenics in TgPrkag3^225Q and Prkag3^-/- mice. The differential gene expression profile was consistent with the physiological differences between the models, providing a molecular mechanism for the observed phenotype. The striking pattern of opposing transcriptional changes between TgPrkag3^225Q and Prkag3^-/- mice identifies differentially expressed targets being truly regulated by AMPK and is consistent with the view that R225Q is an activating mutation, in terms of its downstream effects. Additionally, we identified a wide array of novel targets and regulatory pathways for AMPK in skeletal muscle.

Received for publication, September 23, 2005 , and in revised form, January 9, 2006.

^* This study was supported by the Arexis Research and Development Fund, the Swedish Agency for Innovation Systems, the Swedish Medical Research Council, and the Swedish Foundation for Strategic Research. 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text, Table SI, and Fig. S1.

¹ To whom correspondence should be addressed. Tel.: 46-31-749-1126; Fax: 46-31-749-1101; E-mail: margit.mahlapuu{at}arexis.com.

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

This article has been cited by other articles:

				M. Yoshioka, A. Boivin, C. Bolduc, and J. St-Amand Gender difference of androgen actions on skeletal muscle transcriptome J. Mol. Endocrinol., August 1, 2007; 39(2): 119 - 133. [Abstract] [Full Text] [PDF]

				B. J. Krawiec, G. J. Nystrom, R. A. Frost, L. S. Jefferson, and C. H. Lang AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1555 - E1567. [Abstract] [Full Text] [PDF]