A FoxO1-dependent, but NRF2-independent induction of heme oxygenase-1 during muscle atrophy

FEBS Lett. 2014 Jan 3;588(1):79-85. doi: 10.1016/j.febslet.2013.11.009. Epub 2013 Nov 20.

Abstract

Skeletal muscle plays key roles in metabolic homeostasis. Loss of muscle mass, called muscle atrophy exacerbates disease-associated metabolic perturbations. In this study, we characterized the molecular functions and mechanisms underlying regulation of skeletal muscle atrophy induced by denervation. Denervation significantly increased the expression of heme oxygenase-1 (HO-1) and atrogenes in skeletal muscle. Forkhead box protein O1 (FoxO1) drastically increased in atrophied muscle and selectively stimulated HO-1 gene transcription through direct DNA binding. Lack of HO-1 substantially attenuated muscle atrophy, whereas HO-1 overexpression caused muscle damage in vitro and in vivo. Collectively, HO-1 induced by FoxO1 may cause skeletal muscle atrophy.

Keywords: FoxO1; MAFbx; MuRF1; NRF2; Nerve injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Denervation
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Gene Expression
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism*
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Genetic
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / metabolism
  • Muscular Atrophy / genetics
  • Muscular Atrophy / metabolism*
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism*
  • Protein Binding
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sciatic Nerve / injuries
  • Sciatic Nerve / physiopathology

Substances

  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Heme Oxygenase-1