| First Author | Sopariwala DH | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 10237 |
| PubMed ID | 28860475 | Mgi Jnum | J:255794 |
| Mgi Id | MGI:6108588 | Doi | 10.1038/s41598-017-10238-9 |
| Citation | Sopariwala DH, et al. (2017) Long-term PGC1beta overexpression leads to apoptosis, autophagy and muscle wasting. Sci Rep 7(1):10237 |
| abstractText | Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1alpha) and its splice variant PGC1alpha4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1beta, on muscle size is unclear. In transgenic mice selectively over-expressing PGC1beta in the skeletal muscle, we have found that PGC1beta progressively decreases skeletal muscle mass predominantly associated with loss of type 2b fast-twitch myofibers. Paradoxically, PGC1beta represses the ubiquitin-proteolysis degradation pathway genes resulting in ubiquitinated protein accumulation in muscle. However, PGC1beta overexpression triggers up-regulation of apoptosis and autophagy genes, resulting in robust activation of these cell degenerative processes, and a concomitant increase in muscle protein oxidation. Concurrently, PGC1beta up-regulates apoptosis and/or autophagy transcriptional factors such as E2f1, Atf3, Stat1, and Stat3, which may be facilitating myopathy. Therefore, PGC1beta activation negatively affects muscle mass over time, particularly fast-twitch muscles, which should be taken into consideration along with its known aerobic effects in the skeletal muscle. |
