TNF‐α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle
Top Cited Papers
Open Access
- 20 December 2004
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 19 (3), 362-370
- https://doi.org/10.1096/fj.04-2364com
Abstract
Atrogin1/MAFbx is an ubiquitin ligase that mediates muscle atrophy in a variety of catabolic states. We recently found that H2O2 stimulates atrogin1/MAFbx gene expression. Since the cytokine tumor necrosis factor‐α (TNF‐α) stimulates both reactive oxygen production and general activity of the ubiquitin conjugating pathway, we hypothesized that TNF‐α would also increase atrogin1/MAFbx gene expression. As with H2O2, we found that TNF‐α exposure up‐regulates atrogin1/MAFbx mRNA within2hin C2C12 myotubes. Intraperitoneal injection of TNF‐α increased atrogin1/MAFbx mRNA in skeletal muscle of adult mice within 4 h. Exposing myotubes to either TNF‐α or H2O2 also produced general activation of the mitogen‐activated protein kinases (MAPKs): p38, ERK1/2, and JNK. The increase in atrogin1/MAFbx gene expression induced by TNF‐α was not altered significantly by ERK inhibitor PD98059 or the JNK inhibitor SP600125. In contrast, atrogin1/MAFbx up‐regulation and the associated increase in ubiquitin conjugating activity were both blunted by p38 inhibitors, either SB203580 or curcumin. These data suggest that TNF‐α acts via p38 to increase atrogin1/MAFbx gene expression in skeletal muscle.—Li, Y.‐P., Chen, Y., John, J., Moylan, J., Jin, B., Mann, D. L., Reid, M. B. TNF‐α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 19, 362–370 (2005)Keywords
Funding Information
- National Institutes of Health (AR049022, HL59878, HL58081, HL61543, HL42250-10/10, GM59203)
- National Space Biomedical Research Institute
- Muscular Dystrophy Association
This publication has 46 references indexed in Scilit:
- The IGF-1/PI3K/Akt Pathway Prevents Expression of Muscle Atrophy-Induced Ubiquitin Ligases by Inhibiting FOXO Transcription FactorsMolecular Cell, 2004
- Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injectionFEBS Letters, 2003
- TNF‐α increases ubiquitin‐conjugating activity in skeletal muscle by up‐regulating UbcH2/E220kThe FASEB Journal, 2003
- Sublethal Hemorrhage Induces Tolerance in Animals Exposed to Cecal Ligation and Puncture by Altering p38, p44/42, and SAPK/JNK MAP Kinase ActivationSurgical Infections, 2003
- Oxidative stress in muscular atrophyPublished by Elsevier BV ,2000
- PD 098059 Is a Specific Inhibitor of the Activation of Mitogen-activated Protein Kinase Kinase in Vitro and in VivoPublished by Elsevier BV ,1995
- SB 203580 is a specific inhibitor of a MAP kinase homologue which is stimulated by cellular stresses and interleukin‐1FEBS Letters, 1995
- Sepsis-induced myofibrillar protein catabolism in rat skeletal muscleLife Sciences, 1994
- Tumour necrosis factor‐α increases the ubiquitinization of rat skeletal muscle proteinsFEBS Letters, 1993
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970