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Evidence of apoptosis in skeletal muscle of young and old mice following ischemia‐reperfusion injury
Author(s) -
Hammers David Wayne,
Adamo Martin L,
Walters Tom J,
Farrar Roger P
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.954.5
Subject(s) - poly adp ribose polymerase , apoptosis , skeletal muscle , ischemia , blot , reperfusion injury , gastrocnemius muscle , caspase 3 , endocrinology , medicine , caspase , andrology , chemistry , biology , anatomy , polymerase , enzyme , programmed cell death , biochemistry , gene
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.