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Dysregulation of dysferlin during 7 days mechanical unloading is mediated by ROS in rat soleus muscle (1102.27)
Author(s) -
Lee Yang,
Lawler Matthew,
Botchlett Rachel,
Hord Jeff,
Lawler John
Publication year - 2014
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.28.1_supplement.1102.27
Subject(s) - sarcolemma , dysferlin , oxidative stress , chemistry , reactive oxygen species , microbiology and biotechnology , superoxide dismutase , muscle atrophy , biochemistry , medicine , endocrinology , skeletal muscle , biology , membrane , gene
Dysferlin plays an important role in membrane repair of damaged sarcolemma, is bound to neuronal nitric oxide synthase‐mu (nNOSµ) during disuse, and can be regulated by reactive oxygen species (ROS). Previously, we showed that oxidative stress increased caveolin‐3 which contributed to nNOSµ dislocation from the sarcolemma and thus atrophy. However, the underlying mechanisms that contribute to nNOS translocation and muscle atrophy remain unknown. We hypothesized that oxidative stress would affect dysferlin localization during mechanical unloading, and thus nNOSµ translocation. F344 rats were divided (n=9/group) into control (CON), hindlimb unloaded for 7days (7DHU), and 7D HU+ EUK (EUK) groups. The superoxide dismutase/catalase mimetic EUK‐134 was injected daily (3 mg/kg/d) beginning 24 hours prior to HU. Upregulated ROS sources included sarcolemma (Nox2) and mitochondria (Nox4) during 7DHU were downregulated by EUK‐134. Dystrophin and beta‐sarcoglycan are not altered during 7 days mechanical unloading period. However, nNOS was translocated from sarcolemma to sarcoplasm in 7DHU group. Dysferlin was also downregulated and disrupted from sarcolemma in 7DHU groups, which might exacerbate perturbation of the membrane environment. EUK‐134 partially prevented translocation or nNOS and dysregulation of dysferlin, suggesting changes in these proteins were redox dependent. Our data indicated that oxidative stress is involved in unloading‐induced nNOSµ translocation that is coupled with dysferlin in the rat soleus. Grant Funding Source : Supported by NASA Space Biology grant (NNX12AR62G)