Heart failure increases atrogin-1 and MuRF1 gene expression in skeletal muscle with fiber type-specific atrophy.
Heart failure (HF) is characterized by a reduced tolerance to exercise due to early fatigue and dyspnea; this may be due in part to skeletal muscle myopathy with a shift from slow to fast fibers and loss of muscle mass. Muscle wasting does not occur similarly in all types of muscle fiber, thus we tested the hypothesis that HF induces skeletal muscle atrophy in a fiber type-specific manner altering the expression of atrogin-1 and MuRF1 in a fast muscle of rats with monocrotaline-induced heart failure. We studied extensor digitorum longus (EDL) muscle from both HF and control Wistar rats. Atrogin-1 and MuRF1 mRNA content were determined using Real-Time RT-qPCR while muscle fiber cross-sectional area (CSA) from sections stained histochemically for myofibrillar ATPase were used as an index of type-specific fiber atrophy. The measurement of gene expression by RT-qPCR revealed that EDL muscle mRNA expression of MuRF1 and atrogin-1 was significantly increased in the HF group. Muscle fiber type IIB CSA decreased in the HF group compared to the CT group; there was no significant difference in muscle fiber types I and IIA/D CSA between the HF and CT groups. In conclusion, we showed that HF induces fiber type IIB specific atrophy, up-regulating atrogin-1 and MuRF1 mRNA expression in EDL muscle of monocrotaline treated rats.
Carvalho
Robson Francisco
RF
Department of Morphology, Institute of Biosciences, UNESP São Paulo State University, 18618-000, Botucatu, SP, Brazil. rcarvalho@ibb.unesp.br
Castan
Eduardo Paulino
EP
Coelho
Cesar Augusto
CA
Lopes
Francis Silva
FS
Almeida
Fernanda Losi Alves
FL
Michelin
Aline
A
de Souza
Rodrigo Wagner Alves
RW
Araújo
João Pessoa
JP
Cicogna
Antonio Carlos
AC
Dal Pai-Silva
Maeli
M
D000818:Animals; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology; D008297:Male; D016686:Monocrotaline; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D009133:Muscular Atrophy / Q000235:genetics* / Q000473:pathology; D009928:Organ Specificity / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase 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
D009124:Muscle Proteins; D000070584:Tripartite Motif Proteins; D016686:Monocrotaline; C486692:Fbxo32 protein, rat; D044843:SKP Cullin F-Box Protein Ligases; C499086:Trim63 protein, rat; D044767:Ubiquitin-Protein Ligases