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Skeletal muscle atrophy in critical illness myopathy is associated with muscle fiber type specific apoptotic responses
Author(s) -
Barnes Benjamin Thomas,
Rich Mark M,
Ferry Amy Lynn,
DupontVersteegden Esther Elizabeth
Publication year - 2010
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.24.1_supplement.1046.1
Subject(s) - soleus muscle , apoptosis , atrophy , medicine , endocrinology , muscle atrophy , myopathy , skeletal muscle , hsp70 , tunel assay , chemistry , caspase 3 , heat shock protein , biology , biochemistry , programmed cell death , gene
Critical illness myopathy (CIM) is associated with severe loss of skeletal muscle mass. The purpose of this study was to evaluate the role of apoptosis in soleus and tibialis anterior (TA) muscles using a rat model. CIM was induced by sciatic nerve transection and dexamethasone treatment (5 mg/kg/day, 7–10 days) and resulted in 65% and 54% decrease in TA and soleus muscle mass, resp. Apoptosis was increased in CIM by 320% and 417% assessed by ELISA, and 898% and 667% measured by TUNEL, in soleus and TA, resp. Caspase‐3 and ‐8 activities were elevated 2.6‐ and 2.8‐fold, resp., in TA of CIM rats, while no changes were observed in caspase‐9 and ‐12. Also, no changes in caspase activities were observed with CIM in soleus. Abundance of heat shock protein (HSP)‐27 and HSP70 was 8.6 and 4.9‐fold higher in soleus compared to TA, while no treatment effect was observed. In addition, IP assays showed that HSP70 and uncleaved caspase‐3 interact in both soleus and TA. Caspase‐independent inducers of apoptosis, EndoG and AIF, did not exhibit differences in abundance in the nuclear fraction of soleus or TA, implying that they are not involved in apoptosis with CIM. We conclude that apoptosis contributes to muscle atrophy in CIM, and that TA and soleus utilize different apoptotic pathways, possibly due to elevated HSP expression in soleus. Supported by APS UGSRF (BB) and NS040826 (MR).