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Response of XIAP, ARC, and FLIP apoptotic suppressors to 8 wk of treadmill running in rat heart and skeletal muscle

Laboratory of Muscle Biology and Sarcopenia, Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, West Virginia

Submitted 25 January 2005 ; accepted in final form 10 March 2005

Although it has been demonstrated that exercise training has an antiapoptotic effect on postmitotic myocytes, the mechanisms responsible for this effect are still largely unclear. Because the antiapoptotic effect of exercise training in postmitotic myocytes could be possibly mediated by the upregulation of apoptotic suppressors, this study examined the effect of endurance training on endogenous apoptotic suppressors including X-chromosome-linked inhibitor of apoptosis protein (XIAP), apoptosis repressor with caspases recruitment domain protein (ARC), and FADD-like inhibitor protein (FLIP) in skeletal and cardiac muscles. Eight adult Sprague-Dawley rats were trained 5 days weekly for 8 wk on treadmill, and eight sedentary rats served as controls. Soleus and ventricle muscles were dissected 2 days after the last training session. The mRNA content of XIAP, ARC, and FLIP was estimated by RT-PCR with ribosomal 18S RNA used as an internal control. The protein expression of XIAP, ARC, FLIP_S, and FLIP was assessed by Western immunoblot. After training, mRNA content of ARC and FLIP was not different between the control and trained animals, whereas XIAP mRNA content was elevated by 22 and 14% in the trained soleus and cardiac muscles, respectively, relative to the control samples. No difference was found in the protein content of FLIP_S and FLIP between control and trained muscles, whereas XIAP and ARC protein content was increased by 18 and 38%, respectively, in the soleus muscle of trained animals. Furthermore, negative relationships were found between XIAP and apoptotic DNA fragmentation as well as ARC and caspase-3 activity. These findings are consistent with the hypothesis that the modulation of apoptotic suppressors is involved in training-induced attenuation of apoptosis in skeletal and cardiac muscles.

exercise; mitochondria; cell death receptor; apoptotic inhibitors; X-chromosome-linked inhibitor of apoptosis protein; FADD-like inhibitor protein

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