| First Author | Cai D | Year | 2004 |
| Journal | Cell | Volume | 119 |
| Issue | 2 | Pages | 285-98 |
| PubMed ID | 15479644 | Mgi Jnum | J:93894 |
| Mgi Id | MGI:3510082 | Doi | 10.1016/j.cell.2004.09.027 |
| Citation | Cai D, et al. (2004) IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119(2):285-98 |
| abstractText | Muscle wasting accompanies aging and pathological conditions ranging from cancer, cachexia, and diabetes to denervation and immobilization. We show that activation of NF-kappaB, through muscle-specific transgenic expression of activated IkappaB kinase beta (MIKK), causes profound muscle wasting that resembles clinical cachexia. In contrast, no overt phenotype was seen upon muscle-specific inhibition of NF-kappaB through expression of IkappaBalpha superrepressor (MISR). Muscle loss was due to accelerated protein breakdown through ubiquitin-dependent proteolysis. Expression of the E3 ligase MuRF1, a mediator of muscle atrophy, was increased in MIKK mice. Pharmacological or genetic inhibition of the IKKbeta/NF-kappaB/MuRF1 pathway reversed muscle atrophy. Denervation- and tumor-induced muscle loss were substantially reduced and survival rates improved by NF-kappaB inhibition in MISR mice, consistent with a critical role for NF-kappaB in the pathology of muscle wasting and establishing it as an important clinical target for the treatment of muscle atrophy. |
