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Redox Regulation of Caveolin‐3 and MMP‐9 in the Diaphragm of mdx Mice
Author(s) -
Lawler John M,
Hord Jeff M,
Lee Yang,
Joshi Kumar,
Kim JongHee
Publication year - 2011
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.25.1_supplement.lb519
Subject(s) - apocynin , mdx mouse , duchenne muscular dystrophy , oxidative stress , nadph oxidase , chemistry , dystrophin , reactive oxygen species , microbiology and biotechnology , biochemistry , biology , medicine
Duchenne muscular dystrophy (DMD) elicits damage and inflammation in respiratory (e.g., diaphragm) and limb muscles, and is a caused by an x‐linked mutation in the gene encoding for dystrophin, a scaffolding protein of the dystroglycan complex (DGC). While reactive oxygen species (ROS) amplify damage and inflammation, mechanistic links remain elusive. Recent evidence indicates that impaired integrity of the DGC and muscle damage with DMD are dependent upon upregulation of caveolin‐3 and matrix metalloproteinase‐9 (MMP‐9), with NAD(P)H oxidase (Nox) as an ROS source. We tested the hypothesis that elevation of caveolin‐3 and MMP‐9 and dislocation of DGC proteins (a‐syntrophin, nNOS) were redox‐dependent in the diaphragm of mdx mice. We used a salen‐manganese mimetic of SOD and catalase (EUK‐134) and dissociation of Nox subunits (p47phox, gp91phox) via apocynin as interventions. 20 day old wild‐type and mdx mice were assigned to the following groups for 8 days: wild‐type, mdx + saline, mdx + 30 ml/kg/day EUK‐134, mdx + apocynin (1.5 mM in H2O). EUK‐134 attenuated oxidative stress as well as MMP‐9 and caveolin‐3‐positive staining in the mdx diaphragm. EUK‐134 also partially relocalized α‐syntrophin and nNOS in the sarcolemma. Apocynin reduced elevated sarcolemmal localization of p47phox and MMP‐9. These data indicate that redox regulation exacerbates disruption of the DGC with DMD. Supported by NIH ( AR054084 )