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- Title
Multiple signaling pathways regulate contractile activity-mediated PGC-1 α gene expression and activity in skeletal muscle cells.
- Authors
Zhang, Yuan; Uguccioni, Giulia; Ljubicic, Vladimir; Irrcher, Isabella; Iqbal, Sobia; Singh, Kaustabh; Ding, Shuzhe; Hood, David A.
- Abstract
PGC-1 α is an important transcriptional coactivator that plays a key role in mediating mitochondrial biogenesis. Within seconds of the onset of contractile activity, a number of rapid cellular events occur that form part of the initial signaling processes involved in PGC-1 α gene regulation, such as elevations in cytoplasmic calcium, AMPK and p38 activation, and elevated ROS production. We observed that basal levels of PGC-1 α promoter activity were more sensitive to resting Ca2+ levels, compared to ROS, p38 or, AMPK signaling. Moreover, enhanced PGC-1 α transcription and post-translational activity on DNA were a result of the activation of multiple signal transduction pathways during contractile activity of myotubes. AMPK, ROS, and Ca2+ appear to be necessary for the regulation of contractile activity-induced PGC-1 α gene expression, governed partly through p38 MAPK and Ca MKII activity. Whether these signaling pathways are arranged as a linear sequence of events, or as largely independent pathways during contractile activity, remains to be determined.
- Subjects
PGC-1 protein; CALCIUM ions; REACTIVE oxygen species; MITOGEN-activated protein kinases; CELLULAR signal transduction; REGULATION of muscle contraction; GENE expression
- Publication
Physiological Reports, 2014, Vol 2, Issue 5, pn/a
- ISSN
2051-817X
- Publication type
Article
- DOI
10.14814/phy2.12008