title: The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.
abstract: BACKGROUND
  We investigated the mechanism by which the MERG1a K+ channel increases ubiquitin proteasome proteolysis (UPP).
  
  
  METHODS
  Hindlimb suspension and electro-transfer of Merg1a cDNA into mouse gastrocnemius muscles induced atrophy.
  
  
  RESULTS
  Atrophic gastrocnemius muscles of hindlimb-suspended mice express Merg1a, Murf1, and Mafbx genes. Electrotransfer of Merg1a significantly decreases muscle fiber size (12.6%) and increases UPP E3 ligase Murf1 mRNA (2.1-fold) and protein (23.7%), but does not affect Mafbx E3 ligase expression. Neither Merg1a-induced decreased fiber size nor Merg1a-induced increased Murf1 expression is curtailed significantly by coexpression of inactive HR-Foxo3a, a gene encoding a transcription factor known to induce Mafbx expression.
  
  
  CONCLUSIONS
  The MERG1a K+ channel significantly increases expression of Murf1, but not Mafbx. We explored this expression pattern by expressing inactive Foxo3a and showing that it is not involved in MERG1a-mediated expression of Murf1. These findings suggest that MERG1a may not modulate Murf1 expression through the AKT/FOXO pathway.
authors.affiliation: Anatomy Department, Southern Illinois University School of Medicine, 2080 Life Sciences III, 1135 Lincoln Drive, Carbondale, Illinois, 62901, USA; Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Amber L
authors.initials: AL
authors.lastname: Pond
authors.forename: Carrie
authors.initials: C
authors.lastname: Nedele
authors.forename: Wen-Horng
authors.initials: WH
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Wang
authors.forename: Claire
authors.initials: C
authors.lastname: Walther
authors.forename: Christine
authors.initials: C
authors.lastname: Jaeger
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Bradley
authors.forename: Huahua
authors.initials: H
authors.lastname: Du
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujita
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Hockerman
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Hannon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000235:genetics*; D018014:Gene Transfer Techniques; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal; D009133:Muscular Atrophy / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; C474033:FoxO3 protein, mouse; D009124:Muscle Proteins; D012333:RNA, Messenger; D000070584:Tripartite Motif Proteins; C486691:Fbxo32 protein, mouse; D044843:SKP Cullin F-Box Protein Ligases; C499084:Trim63 protein, mouse; D044767:Ubiquitin-Protein Ligases
keywords: MAFbx; MuRF1; atrogin-1; mERG1a; skeletal muscle atrophy; ubiquitin-proteasome proteolysis