Multiple signaling pathways regulate contractile activity‐mediated PGC‐1α gene expression and activity in skeletal muscle cells

Physiological Reports

Yuan Zhang¹  Giulia Uguccioni¹  Vladimir Ljubicic¹  Isabella Irrcher¹  Sobia Iqbal¹  Kaustabh Singh¹  Shuzhe Ding² 

[1] School of Kinesiology and Health Science, and Muscle Health Research Centre, York University, Toronto, Ontario, Canada;Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education of China, East China Normal University, Shanghai, China

关键词: AMP kinase;    calcium signaling;    exercise;    mitochondrial biogenesis;    p38 MAP kinase;    reactive oxygen species;    skeletal muscle;   

DOI  :  10.14814/phy2.12008

来源: Wiley

【 摘 要 】

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 Ca²⁺ 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 Ca²⁺ 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.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.