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Redox Regulation of nNOS Translocation and Muscle Atrophy During Short‐term Mechanical Unloading
Author(s) -
Lawler John M,
Kunst Mary,
Joshi Kumar,
Hord Jeff M,
Lee Yang,
Martinez Daniel A
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.1085.3
Subject(s) - sarcolemma , atrophy , chromosomal translocation , chemistry , oxidative stress , superoxide dismutase , muscle atrophy , skeletal muscle , medicine , hindlimb , dystrophin , endocrinology , duchenne muscular dystrophy , biochemistry , biology , gene
Reduced mechanical loading causes substantial atrophy of skeletal muscle. An emerging signaling event during mechanical unloading is the translocation of nNOS from the sarcolemmal dystrophin‐glycoprotein complex (DGC). Clues from Duchenne muscular dystrophy papers implicate NAD(P)H oxidase and caveolin‐3 as accomplices in eliciting DGC perturbations. EUK‐134, a mimetic of superoxide dismutase and catalase, was used to test the causal role of redox signaling in nNOS translocation and muscle atrophy as a result of short‐term (54 hours) hindlimb unloading (HU). Fischer‐344 rats were divided into loaded controls (CON), hindlimb unloaded, and HU + EUK‐134. We found that translocation of nNOS from the sarcolemma occurred with HU, and removal was virtually abolished by EUK‐134. Elevation of caveolin‐3 localization with HU was also attenuated by EUK‐134. In addition, mechanical unloading increased localization of NAD(P)H oxidase subunits gp91 phox (Nox2) and p47 phox and increased oxidative stress (4‐hydroxynonenal), effects also abrogated by EUK‐134. Further, unloading‐induced muscle fiber atrophy and fiber‐type shift from slow to fast were also mitigated by EUK‐134. Our findings indicate that nNOS translocation from the sarcolemma is an early event during mechanical unloading, redox‐dependent, and linked to morphological changes in skeletal muscle. Supported by NIH ( AR054084 ).