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AMPK signaling increases MAFbx/Atrogin‐1 and MuRF1 mRNA in C2C12 myotubes
Author(s) -
Krawiec Brian,
Nystrom Gerald,
Frost Robert,
Lang Charles
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1109
Subject(s) - ampk , endocrinology , medicine , myogenesis , ubiquitin ligase , chemistry , downregulation and upregulation , muscle atrophy , skeletal muscle , c2c12 , amp activated protein kinase , myocyte , microbiology and biotechnology , phosphorylation , biology , ubiquitin , protein kinase a , biochemistry , gene
The hypothesis of the present study was that exposure of muscle cells to agonists of AMPK would increase the mRNA content of the muscle‐specific ubiquitin ligases MAFbx/Atrogin‐1 and MuRF1. C 2 C 12 cells were incubated with incremental doses of AICAR or metformin for 24 hours. Both MAFbx/Atrogin‐1 and MuRF1 increased dose‐dependently in response to these treatments. Incubation with AICAR, metformin, or 2‐deoxy‐D‐glucose (2‐DG) produced time‐dependent alterations in ligase expression. While metformin increased ligase mRNA at later time points, both AICAR and 2‐DG produced a biphasic pattern of expression marked by an acute repression followed by a sustained induction of MAFbx/Atrogin‐1 and MuRF1 gene expression. Culture of cells with AMPK‐activating treatments in conjunction with dexamethasone produced a synergistic effect on ligase expression at latter time points. This response occurred in the absence of dexamethasone‐dependent increases in AMPK expression or activity. These alterations elicited by AMPK activation did not extend to the mRNA content of UBR1/E3αI and UBR2/E3αII. These data suggest activation of AMPK in skeletal muscle results in a specific upregulation of MAFbx/Atrogin‐1 and MuRF1 ‐ responses which recall the atrophic transcriptional program executed during skeletal muscle wasting. Hence AMPK may be a key component of the intercalated network of signaling pathways governing skeletal muscle atrophy, where it modifies anti‐ and pro‐atrophic signals in order to influence gene expression in reaction to catabolic stimuli (supported by GM‐38032).