Back to Search
Start Over
AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells.
- Source :
-
American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2007 Jun; Vol. 292 (6), pp. E1555-67. Date of Electronic Publication: 2007 Jan 30. - Publication Year :
- 2007
-
Abstract
- The hypothesis of the present study was that exposure of differentiated muscle cells to agonists of the AMP-activated protein kinase (AMPK) would increase the mRNA content of the muscle-specific ubiquitin ligases muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1). C(2)C(12) cells were incubated with incremental doses of 5-aminoimidazol-4-carboximide ribonucleoside (AICAR) or metformin for 24 h. Both MAFbx and MuRF1 mRNA increased dose dependently in response to these AMPK activators. AICAR, metformin, and 2-deoxy-d-glucose produced time-dependent alterations in ubiquitin ligase expression, typified by a biphasic pattern of expression marked by an acute repression followed by a sustained induction. AMPK-activating treatments in conjunction with dexamethasone produced a pronounced synergistic effect on ligase mRNA expression at later time points. This cooperative response occurred in the absence of a dexamethasone-dependent increase in AMPK expression or activity, as determined by immunoblotting for phosphorylation and expression of AMPKalpha and its downstream target acetyl-CoA carboxylase (ACC). These responses elicited by AMPK activation singly or in combination with dexamethasone did not extend to the mRNA expression of the UBR box family E3s UBR1/E3alphaI and UBR2/E3alphaII. Treatment with the AMPK inhibitor compound C prevented increases in MAFbx and MuRF1 mRNA in response to serum deprivation, as well as AICAR and dexamethasone treatment individually or jointly. Stimulation of AMPK activity in vivo via AICAR injection increased both MAFbx and MuRF1 mRNA in murine skeletal muscle. These data suggest that activation of AMPK in skeletal muscle results in a specific upregulation of MAFbx and MuRF1, responses that are reminiscent of the proposed atrophic transcriptional program executed under various conditions of skeletal muscle wasting. Therefore, AMPK may be a critical component of the intercalated network of signaling pathways governing skeletal muscle atrophy, where its input acts to modify anti- and proatrophic signals to influence gene expression in reaction to catabolic perturbations.
- Subjects :
- AMP-Activated Protein Kinases
Aminoimidazole Carboxamide administration & dosage
Aminoimidazole Carboxamide analogs & derivatives
Aminoimidazole Carboxamide pharmacology
Animals
Cell Line
Deoxyglucose pharmacology
Dexamethasone pharmacology
Dose-Response Relationship, Drug
Drug Synergism
Energy Metabolism physiology
Glucocorticoids pharmacology
Homeostasis physiology
Metformin administration & dosage
Metformin pharmacology
Multienzyme Complexes antagonists & inhibitors
Protein Kinase Inhibitors pharmacology
Protein Serine-Threonine Kinases antagonists & inhibitors
Ribonucleotides administration & dosage
Ribonucleotides pharmacology
Tripartite Motif Proteins
Ubiquitin-Protein Ligases metabolism
Enzyme Activators pharmacology
Multienzyme Complexes metabolism
Muscle Proteins genetics
Muscle, Skeletal metabolism
Protein Serine-Threonine Kinases metabolism
RNA, Messenger metabolism
SKP Cullin F-Box Protein Ligases genetics
Ubiquitin-Protein Ligases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0193-1849
- Volume :
- 292
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 17264220
- Full Text :
- https://doi.org/10.1152/ajpendo.00622.2006