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Title: Opposite transcriptional regulation in skeletal muscle of AMP-activated protein kinase gamma3 R225Q transgenic versus knock-out mice
Author: Nilsson, Elisabeth C.
Long, Yun Chau
Martinsson, Sofia
Glund, Stephan
García-Roves, Pablo M. (Pablo Miguel)
Svensson, L. Thomas
Andersson, Leif
Zierath, Juleen R.
Mahlapuu, Margit
Keywords: Metabolisme
Esquelet humà
Proteïnes quinases
Human skeleton
Protein kinases
Issue Date: 17-Mar-2006
Publisher: American Society for Biochemistry and Molecular Biology
Abstract: AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimer important for metabolic sensing in all eukaryotes. The muscle-specific isoform of the regulatory gamma-subunit of the kinase, AMPK gamma3, has an important role in glucose uptake, glycogen synthesis, and fat oxidation in white skeletal muscle, as previously demonstrated by physiological characterization of AMPK gamma3 mutant (R225Q) transgenic (TgPrkag3(225Q)) and gamma3 knock-out (Prkag3(-/-)) mice. We determined AMPK gamma3-dependent regulation of gene expression by analyzing global transcription profiles in glycolytic skeletal muscle from gamma3 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.
Note: Reproducció del document publicat a:
It is part of: Journal of Biological Chemistry, 2006, vol. 281, num. 11, p. 7244-7252
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ISSN: 0021-9258
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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