title: Effect of short-term cold exposure on skeletal muscle protein breakdown in rats.
abstract: Although it is well established that carbohydrate and lipid metabolism are profoundly altered by cold stress, the effects of short-term cold exposure on protein metabolism in skeletal muscle are still poorly understood. Because cold acclimation requires that an organism adjust its metabolic flux, and muscle amino acids may be an important energy source for heat production, we hypothesize that muscle proteolysis is increased and protein synthesis is decreased under such a stress condition. Herein, cold exposure for 24 h decreased rates of protein synthesis and increased overall proteolysis in both soleus and extensor digitorum longus (EDL) muscles, but it did not affect muscle weight. An increase in proteolysis was accompanied by hyperactivity of the ubiquitin-proteasome system (UPS) in both soleus and EDL, and Ca(2+)-dependent proteolysis in EDL. Furthermore, muscles of rats exposed to cold showed increased mRNA and protein levels of atrogin-1 and muscle RING finger enzyme-1 (MuRF1). Additionally, cold stress reduced phosphorylation of Akt and Forkhead box class O1 (FoxO1), a well-known effect that increases FoxO translocation to the nucleus and leads to activation of proteolysis. Plasma insulin levels were lower, whereas catecholamines, corticosterone, and thyroid hormones were higher in cold-exposed rats compared with control rats. The present data provide the first direct evidence that short-term cold exposure for 24 h decreases rates of protein synthesis and increases the UPS and Ca(2+)-dependent proteolytic processes, and increases expression of atrogin-1 and MuRF1 in skeletal muscles of young rats. The activation of atrophy induced by acute cold stress seems to be mediated at least in part through the inactivation of Akt/FoxO signaling and activation of AMP-activated protein kinase.
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: L H
authors.initials: LH
authors.lastname: Manfredi
authors.forename: N M
authors.initials: NM
authors.lastname: Zanon
authors.forename: M A
authors.initials: MA
authors.lastname: Garófalo
authors.forename: L C C
authors.initials: LC
authors.lastname: Navegantes
authors.forename: I C
authors.initials: IC
authors.lastname: Kettelhut
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000064:Acclimatization; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003080:Cold Temperature; D058639:Cold-Shock Response; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006728:Hormones / Q000097:blood; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000070584:Tripartite Motif Proteins; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D013049:Spectrin; D000071161:Forkhead Box Protein O1
chemical_list: D055372:AMP-Activated Protein Kinases; D002135:Calcium-Binding Proteins; D002154:Calpain; D002352:Carrier Proteins; D051858:Forkhead Transcription Factors; D006728:Hormones; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D046988:Proteasome Endopeptidase Complex; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D044843:SKP Cullin F-Box Protein Ligases; D000070584:Tripartite Motif Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D013049:Spectrin; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1; C033668:calpastatin; C486692:Fbxo32 protein, rat; C499086:Trim63 protein, rat; C449002:mu-calpain
keywords: atrogin-1; cold; muscle RING finger enzyme-1; protein degradation; protein synthesis