Evidence of apoptosis in skeletal muscle of young and old mice following ischemia‐reperfusion injury
Abstract
We have previously shown that tourniquet (TK)‐induced ischemia‐reperfusion (I/R) injury results in larger decrements in mass, morphology, and function in aged skeletal muscle compared to young. To investigate whether apoptosis is also increased in muscles from aged rodents subjected to TK‐induced I/R, the gastrocnemius muscles of 6 mo (young) and 24 mo (old) C57BL mice were analyzed for biochemical markers of apoptosis, namely cleavage of caspase‐3 and poly(ADP‐ribose) polymerase (PARP), a downstream target of active caspase‐3, by Western blotting. I/R resulted in 22 and 7‐fold increases in caspase‐3 cleavage (compared to contralateral control limbs) in young at 5 and 7 days post‐TK, respectively, and 21 and 43‐fold in old at days 5 and 7, respectively (p = 0.05 for all groups). Similarly, there were significant I/R‐induced increases in PARP cleavage in young at day 5 (28‐fold), and in old at days 5 and 7 (26 and 28‐fold; p = 0.05). Total PARP increased in the young following TK but not in the old, resulting in a significant increase in the cleaved to total PARP ratio in old compared to the young I/R samples (p = 0.05) at day 5. These data demonstrate that apoptosis‐mediating pathways are highly activated in skeletal muscle following I/R injury, and provide evidence this may be exacerbated in aged muscle at the 5 day recovery time point. This work funded in part by the U.S. Army Medical Research and Materiel Command grant DAMD17‐03‐1‐0735 to RPF.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2009
- Source ID
- 10.1096/fasebj.23.1_supplement.954.5
Entities
People
- David Wayne Hammers
- Martin L. Adamo
- Roger P. Farrar
- Tom J Walters
Organizations
- United States Army Medical Research and Development Command
- University of Tennessee Health Science Center
- University of Texas at Austin