[PMID]: | 28592414 |
[Au] Autor: | Fajardo VA; Rietze BA; Chambers PJ; Bellissimo C; Bombardier E; Quadrilatero J; Tupling AR |
[Ad] Endereço: | Department of Kinesiology, University of Waterloo, Waterloo Ontario, Canada. |
[Ti] Título: | Effects of sarcolipin deletion on skeletal muscle adaptive responses to functional overload and unload. |
[So] Source: | Am J Physiol Cell Physiol;313(2):C154-C161, 2017 Aug 01. |
[Is] ISSN: | 1522-1563 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca -ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses, we performed soleus and gastrocnemius tenotomy in wild-type (WT) and -null ( ) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles. In the WT overloaded plantaris, we observed ectopic expression of SLN, myofiber hypertrophy, increased fiber number, and a fast-to-slow fiber type shift, which were associated with increased calcineurin signaling (NFAT dephosphorylation and increased stabilin-2 protein content) and reduced SERCA activity. In the WT tenotomized soleus, we observed a 14-fold increase in SLN protein, myofiber atrophy, decreased fiber number, and a slow-to-fast fiber type shift, which were also associated with increased calcineurin signaling and reduced SERCA activity. Genetic deletion of altered these physiological outcomes, with the overloaded plantaris myofibers failing to grow in size and number, and transition towards the slow fiber type, while the unloaded soleus muscles exhibited greater reductions in fiber size and number, and an accelerated slow-to-fast fiber type shift. In both the overloaded and unloaded muscles, these findings were associated with elevated SERCA activity and blunted calcineurin signaling. Thus, SLN plays an important role in adaptive muscle remodeling potentially through calcineurin stimulation, which could have important implications for other muscle diseases and conditions. |
[Mh] Termos MeSH primário: |
Calcineurina/metabolismo Proteínas Musculares/genética Músculo Esquelético/metabolismo Proteolipídeos/genética
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[Mh] Termos MeSH secundário: |
Animais Regulação da Expressão Gênica Seres Humanos Camundongos Camundongos Knockout Fibras Musculares de Contração Rápida/metabolismo Fibras Musculares de Contração Lenta/metabolismo Proteínas Musculares/metabolismo Músculo Esquelético/fisiologia Músculo Esquelético/cirurgia Proteolipídeos/metabolismo ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo Tenotomia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Muscle Proteins); 0 (Proteolipids); 145018-73-1 (sarcolipin); EC 3.1.3.16 (Calcineurin); EC 3.6.3.8 (Sarcoplasmic Reticulum Calcium-Transporting ATPases) |
[Em] Mês de entrada: | 1708 |
[Cu] Atualização por classe: | 170814 |
[Lr] Data última revisão:
| 170814 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170609 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1152/ajpcell.00291.2016 |
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