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Decreased induction of heat‐shock proteins with age in ischemia‐reperfusion injured skeletal muscle
Author(s) -
Hammers David W,
Adamo Martin,
Walters Tom,
Farrar Roger P
Publication year - 2008
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.22.1_supplement.1163.15
Subject(s) - heat shock protein , anabolism , downregulation and upregulation , western blot , skeletal muscle , hsp70 , hindlimb , ischemia , endocrinology , medicine , andrology , heat shock , biology , chemistry , biochemistry , gene
Heat shock proteins (HSPs) are molecular chaperones that are upregulated to stabilize cellular proteins in response to stress. Previously, our laboratory has demonstrated that tourniquet (TK)‐induced ischemia‐reperfusion injury (I/R) is a clinically relevant perturbation to skeletal muscle with age‐related differences in recovery. To investigate the role of HSPs in the age‐related differential recovery to I/R, 6 month‐old (Young) and 24 month‐old (Old) C57BL mice were subjected to 2 hour TK‐induced I/R of the hind limb, and separated into either 1, 3, 5, or 7‐day recovery groups. H&E staining confirms greater damage in Old in response to I/R at days 3, 5, and 7. Western blot analysis reveals a significant upregulation of HSP 70 in both Young and Old 1 day post‐TK, however HSP 70 content continues to increase another 4‐fold by day 7 in Young, while there is no increase beyond day 1 in Old. This suggests the protective effect of HSP 70 is less in Old, allowing more damage to occur compared to Young. In addition, significantly lower phosphorylation of mTOR and FoxO proteins is demonstrated in Old 7 days post‐TK, suggesting reduced anabolic signaling coupled with elevated protein catabolism is responsible for the impaired recovery with age. This work funded in part by the U.S. Army Medical Research and Material Command grant DAMD17‐03‐1‐0735 to RPF.