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Inhibition of calpain or caspase‐3 protects against immobilization‐induced muscle atrophy
Author(s) -
Talbert Erin E,
Smuder Ashley J,
Min Kisuk,
Kwon Oh-Sung,
Powers Scott K.
Publication year - 2012
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.26.1_supplement.1075.7
Subject(s) - calpain , muscle atrophy , atrophy , soleus muscle , medicine , caspase , endocrinology , chemistry , skeletal muscle , mitochondrion , microbiology and biotechnology , apoptosis , caspase 12 , proteolysis , caspase 3 , biochemistry , biology , enzyme , programmed cell death
Increased proteolysis is crucial to disuse skeletal muscle atrophy. However, the roles that the proteases calpain and caspase‐3 play during inactivity‐induced muscle atrophy remain unclear. We hypothesized that administering either a calpain or caspase‐3 inhibitor would protect the soleus muscle against atrophy and mitochondrial dysfunction following 7 days of hindlimb immobilization (i.e. casting). Immobilization significantly (~13%) decreased the cross‐sectional area of soleus type I fibers. Importantly, independent inhibition of calpain or caspase‐3 prevented this atrophy. Casting decreased soleus mitochondrial coupling by ~52%. Inhibition of either calpain or caspase‐3 attenuated this casting‐induced mitochondrial dysfunction. Interestingly, inhibition of calpain prevented the casting‐induced activation of caspase‐3. Further, caspase‐3 inhibition prevented the immobilization‐induced activation of calpain. In conclusion, these results indicate that calpain and caspase‐3 play important roles during inactivity‐induced soleus muscle atrophy. Further, our data suggest that there is a regulatory cross‐talk signaling mechanism though which calpain and caspase‐3 regulate the activity of each other. Supported by NIH R01 HL087839 (SKP) and a UF Alumni Fellowship (EET).