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The protective role of PGC‐1α in the recovery of muscle disuse atrophy
Author(s) -
Kang ChoungHun,
Goodman Craig A,
Hornberger Troy A,
Ji Li Li
Publication year - 2013
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.27.1_supplement.940.5
Subject(s) - sod2 , sirt3 , mitochondrial biogenesis , chemistry , oxidative stress , endocrinology , superoxide dismutase , skeletal muscle , medicine , mitochondrion , hindlimb , muscle atrophy , microbiology and biotechnology , biology , acetylation , biochemistry , sirtuin , gene
Prolonged inactivity results in skeletal muscle atrophy including increased reactive oxygen species (ROS) generation, inflammation and protein degradation. Over‐expression of peroxisome proliferator‐activated receptor‐γ coactivator‐1α (PGC‐1α) has been shown to increase mitochondrial biogenesis and reduce oxidative stress. Methods Female FVB/N mice (N=48) were randomly divided into 4 groups: (1) control (CON) & injected with GFP (Con‐GFP); (2) CON & PGC‐1α in vivo transfection (Con‐PGC‐1α); (3) two wks of hindlimb immobilization (IM) followed by 5 days remobilization (IM‐RM) & injected with GFP (IM‐RM‐GFP); and (4) IM‐RM & PGC‐1α in vivo transfection (IM‐RM‐PGC‐1α). GFP or PGC‐1α was injected into tibialis anterior (TA) muscle of one of the hindlimbs with an electroporation system. Results PGC‐1α induced SIRT3 and SOD2 binding in CON and IM‐RM by enhancing SIRT3 promoter activity and protein expression. Basal SOD2 acetylation level was increased by 57% in IM‐RM, however PGC‐1α decreased SOD acetylation by 30% (P<0.05) in IM‐RM. Thus, PGC‐1α over‐expression resulted in a 15% increase in superoxide dismutase (SOD) 2 protein content and activity in IM‐RM vs CON (p<0.05). IM‐RM increased mitochondrial H2O2 generation in both GFP and PGC‐1α groups, whereas PGC‐1α attenuate IM‐RM‐induced ROS generation by 18% (P<0.05).