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Multiple signaling pathways regulate contractile activity-mediated PGC-1α gene expression and activity in skeletal
Yuan Zhang1, Giulia Uguccioni2, Vladimir Ljubicic2
1School of Kinesiology and Health Science, and Muscle Health Research Centre, York University, Toronto, M3J 1P3, Ontario, Canada Department of Sport and Health Science, Nanjing Sport Institute, Nanjing, China Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education of China, East China Normal University, Shanghai, China.
Abstract:
PGC-1α 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-1α gene regulation, such as elevations in cytoplasmic calcium, AMPK and p38 activation, and elevated ROS production. We observed that basal levels of PGC-1α promoter activity were more sensitive to resting Ca(2+) levels, compared to ROS, p38 or, AMPK signaling. Moreover, enhanced PGC-1α 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 Ca(2+) appear to be necessary for the regulation of contractile activity-induced PGC-1α gene expression, governed partly through p38 MAPK and CaMKII 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.