Submitted on January 14, 2008
Accepted on October 1, 2008
MITOCHONDRIAL APOPTOTIC SIGNALING IS ELEVATED IN CARDIAC BUT NOT SKELETAL MUSCLE IN THE OBESE ZUCKER RAT AND IS REDUCED WITH AEROBIC EXERCISE
Jonathan M. Peterson1, Randall W. Bryner2, Amy Sindler3, Jefferson C. Frisbee4, and Stephen E. Alway5*
1 Exercise Physiology, West Virginia University, Morgantown WV, West Virginia, United States
2 Exercise Physiology, West Virginia University, morgantown, Maine, United States
3 Physiology & Pharmacology, West Virginia University, United States
4 Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University, Morgantown, West Virginia, United States
5 Department Exercise Physiology, P.O. Box 9227, West Virginia University School of Medicine, Morgantown, West Virginia, United States
* To whom correspondence should be addressed. E-mail: salway{at}hsc.wvu.edu.
Mitochondrial apoptosis and apoptotic signaling modulations by aerobic training were studied in cardiac and skeletal muscles of obese Zucker rats (OZR), a rodent model of metabolic syndrome. Comparisons were made between left ventricle, soleus, and gastrocnemius muscles from OZR (n=16) and aged matched lean Zucker rats (LZR; n=16) that were untrained (n=8) or aerobically trained on a treadmill for 9 weeks (n=8). Cardiac Bcl-2 protein expression levels were ~50% lower in the OZR compared with the LZR, with no difference in either of the skeletal muscles. Bax protein expression levels were similar in cardiac and skeletal muscles of the OZR compared to the LZR. However, there was a ~7-fold increase in the Bax protein accumulation in the myocardial mitochondrial protein fraction of the OZR compared to the LZR. Additionally, there was an increase in cytochrome c released from the mitochondria, caspase-9 and caspase-3 activity, with a corresponding elevation in DNA fragmentation in the cardiac muscles of the OZR compared to the LZR. Mitochondrial apoptotic signaling was not different in skeletal muscles of OZR and LZR groups. Exercise training reduced cardiac Bax protein levels, the mitochondrial localization of Bax, cytosolic cytochrome c, caspase activity, and DNA fragmentation in cardiac muscles of the OZR after exercise, with no change in the skeletal muscles. These data show that mitochondrial apoptosis is elevated in the cardiac but not skeletal muscles of the OZR, but aerobic exercise training was effective in reducing cardiac mitochondrial apoptotic signaling.
