1. Multiple signaling pathways regulate contractile activity-mediated PGC-1 α gene expression and activity in skeletal muscle cells.
- Author
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Zhang, Yuan, Uguccioni, Giulia, Ljubicic, Vladimir, Irrcher, Isabella, Iqbal, Sobia, Singh, Kaustabh, Ding, Shuzhe, and Hood, David A.
- Subjects
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PGC-1 protein , *CALCIUM ions , *REACTIVE oxygen species , *MITOGEN-activated protein kinases , *CELLULAR signal transduction , *REGULATION of muscle contraction , *GENE expression - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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