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Impaired regeneration in ERRalpha deficient skeletal muscle
Author(s) -
LaBarge Samuel,
McDonald Marisa,
Huss Janice
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.1078.17
Subject(s) - mitochondrial biogenesis , skeletal muscle , myocyte , microbiology and biotechnology , regeneration (biology) , cardiotoxin , biology , endocrinology , mitochondrion , myogenesis , medicine , citrate synthase , biochemistry , enzyme
The nuclear receptor transcription factor, Estrogen‐Related Receptor α (ERRα), regulates mitochondrial glucose and fatty acid oxidation and mitochondrial biogenesis in highly oxidative tissues. However, it is unknown whether ERRα is involved in adaptive skeletal muscle processes requiring metabolic remodeling like muscle regeneration. We employed skeletal muscle‐specific knockout mice (m‐ERRα−/−) to assess ERRα‐dependence of mitochondrial biogenesis and myofiber regeneration in tibialis anterior following cardiotoxin (CTX)‐induced injury. Expression of ERRα and its coactivator, PGC‐1α, were increased in regenerating WT myofibers, supporting their involvement in metabolic and contractile gene regulation during regeneration. Satellite cell (Pax7 + ) activation and macrophage (CD11b + ) infiltration were the same in WT and m‐ERRα−/− injured muscles. In contrast, delayed regeneration in m‐ERRα−/− muscle was revealed by increased centralized nuclei at d15 and reduced myofiber area at d7 and d15 compared to WT mice. Mitochondrial enzyme activities (succinate dehydrogenase, cytochrome oxidase, citrate synthase) were not distinct early (d7) but were significantly lower in d15 m‐ERRα−/− regenerating fibers compared to WT. These results suggest that delayed early regeneration in m‐ERRα−/− muscles is not due to mitochondrial defects but may involve perturbed signaling of MAPK or calcineurin/CaMK pathways, that are modulated by ERRα and involved in muscle regeneration. (Support by NIH R01DK74700 (J.M.H.) and Morgan and Helen Chu graduate fellowship (S.L.)