Premium
Regulation of the ubiquitin proteasome and calpain systems in a dog model of duchenne muscular dystrophy
Author(s) -
Wadosky Kristine M.,
Rodriguez Jessica E.,
Li Luge,
Bogan Dan,
Kornegay Joe N,
Willis Monte S
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.1000.8
Subject(s) - duchenne muscular dystrophy , calpain , skeletal muscle , muscular dystrophy , proteasome , dystrophin , medicine , endocrinology , mdx mouse , muscle atrophy , chemistry , biology , microbiology and biotechnology , biochemistry , enzyme
Duchenne muscular dystrophy (DMD) is an incurable and lethal genetic disorder characterized by progressive muscle wasting caused by the loss of functional dystrophin. Activation of both calpain and the proteasome degradation systems has been reported in the pathogenesis of DMD in skeletal muscle. In fact, calpain and proteasome inhibitors have been used as therapies in mouse models. Here we investigated specific calpain and proteasome activities of 5 skeletal muscles and the left ventricle (LV) in a more severe canine model of DMD (golden retriever muscular dystrophy [GRMD]). The expression of ubiquitin proteasome system components and calpain 1 and 2 were increased in GRMD skeletal muscle generally, but decreased in the LV. We identified significant increases in all three proteasome activities (trypsin‐, chymotrypsin‐, and caspase‐like) in only 1 GRMD muscle and no activation of any proteasome activities in the LV. Calpain 1&2 activities were increased in 2 GRMD skeletal muscles and the LV compared to controls. Furthermore, protease activity of most GRMD skeletal muscles studied correlate with the degree of atrophy and hypertrophy found in the individual muscles. As proteasome and calpain inhibitors continue to be considered as potential therapies for DMD, this work provides evidence for the variable activation of these systems in different skeletal muscles and the heart. Supported by NIH R01HL104129.