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PGC‐1alpha over‐expression alters the proteome of dystrophin deficient skeletal muscle
Author(s) -
Hollinger Katrin,
GardanSalmon Delphine,
Dixon Jenna,
Lonergan Steven,
Selsby Joshua T
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.1051.28
Subject(s) - utrophin , dystrophin , duchenne muscular dystrophy , skeletal muscle , mdx mouse , hindlimb , proteome , biology , gene expression , microbiology and biotechnology , peroxisome proliferator activated receptor , chemistry , endocrinology , gene , biochemistry , genetics
Duchenne muscular dystrophy is characterized by profound muscle injury and is caused by the production of an aberrant dystrophin gene product. In dystrophic muscle peroxisome proliferator‐activated receptor‐gamma coactivator (PGC)‐1alpha appears to reduce muscle injury by increasing expression of the dystrophin‐related protein, utrophin, as well as expression of oxidative proteins. The goal of the current study was to determine the extent to which PGC‐1alpha over‐expression altered the dystrophic proteome. Neonatal mdx mice (n=6) were injected in the right hind limb with adeno‐ associated virus (AAV) driving PGC‐1alpha expression and the left hind limb was injected with an empty AAV vector. After 6 weeks the gastrocnemius was removed, total protein extracted, 2D‐ DIGE performed, and spots differing in abundance analyzed by mass spectroscopy. Forty‐five spots in the 12% gel and 22 spots in the 8% gel were differentially expressed and 16 different proteins were identified. Limbs over‐expressing PGC‐1alpha had lower expression of serotransferrin indicating reduced pro‐oxidant free iron. Additionally, expression of cytoskeletal components was decreased in PGC‐1alpha over‐expressing muscle suggesting that induced utrophin expression stabilized the muscle membrane. These data support the beneficial role of PGC‐1alpha and provide additional insight regarding the underlying mechanism of protection.