000199681 001__ 199681
000199681 005__ 20181203023520.0
000199681 0247_ $$2doi$$a10.1096/fj.13-229211
000199681 022__ $$a0892-6638
000199681 02470 $$2ISI$$a000335324800006
000199681 037__ $$aARTICLE
000199681 245__ $$aEstrogen-related receptor-alpha ( ERR alpha) deficiency in skeletal muscle impairs regeneration in response to injury
000199681 260__ $$aBethesda$$bFederation of American Society of Experimental Biology$$c2014
000199681 269__ $$a2014
000199681 300__ $$a16
000199681 336__ $$aJournal Articles
000199681 520__ $$aThe estrogen-related receptor- (ERR) regulates mitochondrial biogenesis and glucose and fatty acid oxidation during differentiation in skeletal myocytes. However, whether ERR controls metabolic remodeling during skeletal muscle regeneration in vivo is unknown. We characterized the time course of skeletal muscle regeneration in wild-type (M-ERRWT) and muscle-specific ERR-/- (M-ERR-/-) mice after injury by intramuscular cardiotoxin injection. M-ERR-/- mice exhibited impaired regeneration characterized by smaller myofibers with increased centrally localized nuclei and reduced mitochondrial density and cytochrome oxidase and citrate synthase activities relative to M-ERRWT. Transcript levels of mitochondrial transcription factor A, nuclear respiratory factor-2a, and peroxisome proliferator-activated receptor (PPAR)- coactivator (PGC)-1, were downregulated in the M-ERR-/- muscles at the onset of myogenesis. Furthermore, coincident with delayed myofiber recovery, we observed reduced muscle ATP content (-45% vs.M-ERRWT) and enhanced AMP-activated protein kinase (AMPK) activation in M-ERR-/- muscle. We subsequently demonstrated that pharmacologic postinjury AMPK activation was sufficient to delay muscle regeneration in WT mice. AMPK activation induced ERR transcript expression in M-ERRWT muscle and in C2C12 myotubes through induction of the Esrra promoter, indicating that ERR may control gene regulation downstream of the AMPK pathway. Collectively, these results suggest that ERR deficiency during muscle regeneration impairs recovery of mitochondrial energetic capacity and perturbs AMPK activity, resulting in delayed myofiber repair.LaBarge, S., McDonald, M., Smith-Powell, L., Auwerx, J., Huss, J. M. Estrogen-related receptor- (ERR) deficiency in skeletal muscle impairs regeneration in response to injury.
000199681 6531_ $$anuclear receptors
000199681 6531_ $$amitochondria
000199681 6531_ $$amyogenic differentiation
000199681 6531_ $$agene expression
000199681 6531_ $$aAMP-activated protein kinase
000199681 700__ $$aLabarge, Samuel
000199681 700__ $$aMcdonald, Marisa
000199681 700__ $$aSmith-Powell, Leslie$$uCity Hope Natl Med Ctr, Beckman Res Inst, Dept Mol Pharmacol, Duarte, CA 91010 USA
000199681 700__ $$0240040$$aAuwerx, Johan$$g185233
000199681 700__ $$aHuss, Janice M.$$uCity Hope Natl Med Ctr, Beckman Res Inst, Dept Diabet & Metab Dis Res, Duarte, CA 91010 USA
000199681 773__ $$j28$$k3$$q1082-1097$$tFaseb Journal
000199681 909C0 $$0252023$$pNCEM$$xU11905
000199681 909CO $$ooai:infoscience.tind.io:199681$$pSV$$particle
000199681 917Z8 $$x196843
000199681 937__ $$aEPFL-ARTICLE-199681
000199681 973__ $$aOTHER$$rREVIEWED$$sPUBLISHED
000199681 980__ $$aARTICLE