title: αMSH blunts endotoxin-induced MuRF1 and atrogin-1 upregulation in skeletal muscle by modulating NF-κB and Akt/FoxO1 pathway.
abstract: Alpha melanocyte stimulating hormone (αMSH) has been shown to have anti-inflammatory and anticachectic actions. We hypothesized that αMSH administration could attenuate the effect of lipopolysaccharide (LPS) on the skeletal muscle through modifications in IGF-Akt-FoxO1 pathway, or/and in serum corticosterone. Adult male Wistar rats were injected with LPS and/or αMSH. αMSH administration reduced LPS-induced increase in liver TNFα and serum nitrites as well as NF-κB activation in skeletal muscle. In contrast, αMSH was not able to prevent the stimulatory effect of LPS on serum concentration of ACTH and corticosterone. LPS decreased serum levels of IGF-I and IGFBP3 and their expression in the liver (P < 0.01). However IGFBP3 expression in the gastrocnemius was increased by LPS. Treatment with αMSH prevented the effects of LPS on IGFBP3 but not on IGF-I. In the gastrocnemius αMSH blocked LPS-induced decrease in pAkt as well as the increase in pNF-κB(p65), FoxO1, atrogin-1, and MuRF1 levels. These results suggest that αMSH blunts skeletal muscle response to endotoxin by downregulating atrogenes and FoxO1 at least in part by controlling NF-κB activation and Akt signalling, but not through modifications in the secretion of corticosterone or IGF-I.
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Martín
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: Ana Belén
authors.initials: AB
authors.lastname: Gómez-SanMiguel
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gómez-Moreira
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Villanúa
authors.affiliation: Department of Physiology, Faculty of Medicine, Complutense University of Madrid, 28040 Madrid, Spain.
authors.forename: Asunción
authors.initials: A
authors.lastname: López-Calderón
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015151:Immunoblotting; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000521:alpha-MSH / Q000494:pharmacology*; D000071161:Forkhead Box Protein O1
chemical_list: D003345:Corticosterone; D051858:Forkhead Transcription Factors; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D051057:Proto-Oncogene Proteins c-akt; D044843:SKP Cullin F-Box Protein Ligases; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D000521:alpha-MSH; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C486692:Fbxo32 protein, rat; C499086:Trim63 protein, rat