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Metallothionein (MT) expression increases in skeletal muscle following tourniquet‐induced ischemia/reperfusion (I/R) injury
Author(s) -
Urso Maria Laina,
Szelenyi Eric R,
Walters Thomas J
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.730.3
Subject(s) - skeletal muscle , matrix metalloproteinase , calpain , metallothionein , pi3k/akt/mtor pathway , chemistry , oxidative stress , downregulation and upregulation , reperfusion injury , endocrinology , medicine , ischemia , biology , signal transduction , biochemistry , enzyme , gene
Increased MT and extracellular matrix (ECM) metalloprotease (MMP) activity has been documented in skeletal muscle following trauma. MTs bind zinc and MMPs, possibly affecting activation of the zinc‐dependent mTOR pathway and MMP‐dependent tissue repair post‐injury. Tourniquet (TK) application is used to control bleeding post‐injury, although I/R episodes associated with TK use result in skeletal muscle proteolysis. This study investigated TK‐induced I/R injury on MT, MMP, and mTOR pathway activation in rat extensor digitorum longus (EDL). A TK was applied to the hind limb of 14 male rats for 3 h, and then deflated, resulting in I/R injury. EDLs were harvested 2 h post‐reperfusion for analysis. I/R resulted in a significant (p<0.05) upregulation of MT (4.7‐ fold) and MMP‐9 (2.6‐ fold) mRNA, with no change in MMP‐2. Immunoblot analysis revealed that protein levels of MT were increased 24 ± 11.1 % (p<0.05). The mTOR protein level, its phosphorylation on Ser2448, and the activity of S6K1 were unaffected 2 h post‐I/R injury. Immunohistochemistry confirmed results. MT production is likely related to I/R‐induced oxidative‐stress, which potentially affects ECM integrity, explaining our observed increase in MMP‐9. These data suggest that oxidative‐mediated ECM disruption is a potential mechanism for increased skeletal muscle proteolysis in response to TK‐induced I/R‐injury.