Mild Heat Stress Induces Mitochondrial Biogenesis by Activating AMPK-SIRT1- PGC-1alpha Pathway in C2C12 Myotubes
THURSDAY, SEPTEMBER 23, 2010, 1:00-3:00PM POSTER SESSION 1: Board #43: Exercise, Oxidative Stress, and Redox Signaling
University of California, Berkeley, Berkeley, CA.
During exercise, a large portion of energy derived from the oxidation of metabolic fuels is dissipated as heat. The temperature of exercising muscles can rise above 40°C and the prevention of heat injury is an important issue in exercise physiology. Although severe heat injury can be lethal, several beneficial effects of mild heat stress have been reported. Among all stimuli induced by exercise, the net effects of mild heat stress on mitochondria are least characterized. PURPOSE: To determine the effects of mild heat stress on mitochondrial biogenesis and its mechanisms. METHODS: C2C12 myotubes were exposed to a mild heat stress (40°C for 1 hour) per day for 1 or 5 days. After 1 or 24 hours after the last treatment, myotubes were harvested for measurements of mRNA level, protein expression and promoter activity. All data was derived from at least three independent experiments. RESULTS: One hour of mild heat stress increased the mRNA expression of several regulatory and structural genes involved in mitochondrial biogenesis. In addition, one hour of mild heat stress up-regulated the expression of Silent Information Regulator T1 (SIRT1) and phosphorylation of AMP-activated protein kinase (AMPK) at threonine 172. The promoter activity of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) was also up-regulated by mild heat stress. Five days of mild heat stress up-regulated mitochondrial oxidative phosphorylation proteins including ATP synthase subunit alpha, Complex IV subunit I, Complex III subunit Core 2, Complex II subunit 30kDa, and Complex I subunit NDUFB8. CONCLUSION: Mild heat stress induces mitochondrial biogenesis by activating the AMPK-SIRT1-PGC-1alpha pathway in C2C12 myotubes. Hence, modest increase in the temperature of active muscles may also contribute to the well-defined adaptive responses of muscle to exercise.© 2010 American College of Sports Medicine