Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 QUICK SEARCH:   [advanced]


     


Am J Physiol Cell Physiol (May 19, 2004). doi:10.1152/ajpcell.00425.2003
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/3/C790    most recent
00425.2003v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Akimoto, T.
Right arrow Articles by Yan, Z.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Akimoto, T.
Right arrow Articles by Yan, Z.
Submitted on October 2, 2003
Accepted on May 13, 2004

Real-time Imaging of Peroxisome Proliferator Activated Receptor {gamma} Co-activator-1{alpha} Promoter Activity in Skeletal Muscles of Living Mice

Takayuki Akimoto1, Brian S Sorg2, and Zhen Yan1*

1 Medicine, Duke University Medical Center, Durham, NC, USA
2 Radiation Oncology, Duke University Medical Center, Durham, NC, USA

* To whom correspondence should be addressed. E-mail: zhen.yan{at}duke.edu.

In response to sustained increase in contractile activity, mammalian skeletal muscle undergoes adaptation with enhanced mitochondrial biogenesis and fiber type switching. The peroxisome proliferator activated receptor {gamma} co-activator-1{alpha} (PGC-1{alpha}) has recently been identified as a key regulator for these adaptive processes. To investigate the sequence elements in the PGC-1{alpha} gene that are responsible for activity-dependent transcriptional activation, we have established a unique system to analyze promoter activity in skeletal muscle of living mice. Expression of PGC-1{alpha}-firefly luciferase reporter gene in mouse tibialis anterior (TA) muscle transfected by electric pulse-mediated gene transfer was assessed repeatedly in the same muscle by optical bioluminescence imaging analysis before and after low-frequency (10 Hz) motor nerve stimulation. Nerve stimulation (2 h) resulted in a transient 3-fold increase (P<0.05) in PGC-1{alpha} promoter activity along with a 1.6-fold increase (P<0.05) in endogenous PGC-1{alpha} mRNA. Mutation of two consensus myocyte enhancer factor 2 (MEF2) binding sites (-2901 and -1539) or a cAMP response element (CRE) (-222) completely abolished nerve stimulation-induced increase in PGC-1{alpha} promoter activity. These findings provide direct evidence that contractile activity-induced PGC-1{alpha} promoter activity in skeletal muscle is dependent on the MEF2 and the CRE sequence elements. The experimental methods used here have general applicability to studies of gene regulation in muscle.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.