| Title: |
PGC-1 alpha a protects skeletal muscle from atrophy by suppressing Fox03 action and atrophy-specific gene transcription |
| Authors: |
SANDRI, MARCO; LIN JD; HANDSCHIN C; YANG WL; ARANY ZP; LECKER SH; GOLDBERG AL; SPIEGELMAN BM |
| Contributors: |
Sandri, Marco; Lin, Jd; Handschin, C; Yang, Wl; Arany, Zp; Lecker, Sh; Goldberg, Al; Spiegelman, Bm |
| Publisher Information: |
National Academy of Sciences:2101 Constitution Avenue Northwest:Washington, DC 20418:(877)314-2253, (615)377-3322, EMAIL: subspnas@nas.edu, INTERNET: http://www.pnas.org, Fax: (615)377-0525 |
| Publication Year: |
2006 |
| Collection: |
Padua Research Archive (IRIS - Università degli Studi di Padova) |
| Description: |
Maintaining muscle size and fiber composition requires contractile activity. Increased activity stimulates expression of the transcriptional coactivator PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1alpha), which promotes fiber-type switching from glycolytic toward more oxidative fibers. In response to disuse or denervation, but also in fasting and many systemic diseases, muscles undergo marked atrophy through a common set of transcriptional changes. FoxO family transcription factors play a critical role in this loss of cell protein, and when activated, FoxO3 causes expression of the atrophy-related ubiquitin ligases atrogin-1 and MuRF-1 and profound loss of muscle mass. To understand how exercise might retard muscle atrophy, we investigated the possible interplay between PGC-1alpha and the FoxO family in regulation of muscle size. Rodent muscles showed a large decrease in PGC-1alpha mRNA during atrophy induced by denervation as well as by cancer cachexia, diabetes, and renal failure. Furthermore, in transgenic mice overexpressing PGC-1alpha, denervation and fasting caused a much smaller decrease in muscle fiber diameter and a smaller induction of atrogin-1 and MuRF-1 than in control mice. Increased expression of PGC-1alpha also increased mRNA for several genes involved in energy metabolism whose expression decreases during atrophy. Transfection of PGC-1alpha into adult fibers reduced the capacity of FoxO3 to cause fiber atrophy and to bind to and transcribe from the atrogin-1 promoter. Thus, the high levels of PGC-1alpha in dark and exercising muscles can explain their resistance to atrophy, and the rapid fall in PGC-1alpha during atrophy should enhance the FoxO-dependent loss of muscle mass. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
info:eu-repo/semantics/altIdentifier/wos/WOS:000241879500037; volume:103; firstpage:16260; lastpage:16265; journal:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; https://hdl.handle.net/11577/153741 |
| Availability: |
https://hdl.handle.net/11577/153741 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.2B88A116 |
| Database: |
BASE |