Sopariwala Danesh H, Pant Meghna, Shaikh Sana A, Goonasekera Sanjeewa A, Molkentin Jeffery D, Weisleder Noah, Ma Jianjie, Pan Zui, Periasamy Muthu
Department of Physiology and Cell Biology, College of Medicine, The Ohio State University, Columbus, Ohio;
Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio;
J Appl Physiol (1985). 2015 Apr 15;118(8):1050-8. doi: 10.1152/japplphysiol.01066.2014. Epub 2015 Feb 19.
Sarcolipin (SLN) is a regulator of sarcoendoplasmic reticulum calcium ATPase in skeletal muscle. Recent studies using SLN-null mice have identified SLN as a key player in muscle thermogenesis and metabolism. In this study, we exploited a SLN overexpression (Sln(OE)) mouse model to determine whether increased SLN level affected muscle contractile properties, exercise capacity/fatigue, and metabolic rate in whole animals and isolated muscle. We found that Sln(OE) mice are more resistant to fatigue and can run significantly longer distances than wild-type (WT). Studies with isolated extensor digitorum longus (EDL) muscles showed that Sln(OE) EDL produced higher twitch force than WT. The force-frequency curves were not different between WT and Sln(OE) EDLs, but at lower frequencies the pyruvate-induced potentiation of force was significantly higher in Sln(OE) EDL. SLN overexpression did not alter the twitch and force-frequency curve in isolated soleus muscle. However, during a 10-min fatigue protocol, both EDL and soleus from Sln(OE) mice fatigued significantly less than WT muscles. Interestingly, Sln(OE) muscles showed higher carnitine palmitoyl transferase-1 protein expression, which could enhance fatty acid metabolism. In addition, lactate dehydrogenase expression was higher in Sln(OE) EDL, suggesting increased glycolytic capacity. We also found an increase in store-operated calcium entry (SOCE) in isolated flexor digitorum brevis fibers of Sln(OE) compared with WT mice. These data allow us to conclude that increased SLN expression improves skeletal muscle performance during prolonged muscle activity by increasing SOCE and muscle energetics.
肌浆球蛋白（SLN）是骨骼肌肌浆网钙ATP酶的一种调节因子。最近使用SLN基因敲除小鼠的研究已确定SLN是肌肉产热和代谢的关键参与者。在本研究中，我们利用SLN过表达（Sln（OE））小鼠模型来确定SLN水平升高是否会影响全动物和分离肌肉的肌肉收缩特性、运动能力/疲劳以及代谢率。我们发现Sln（OE）小鼠比野生型（WT）小鼠更抗疲劳，并且能跑的距离明显更长。对分离的趾长伸肌（EDL）肌肉的研究表明，Sln（OE）EDL产生的抽搐力比WT更高。WT和Sln（OE）EDL之间的力-频率曲线没有差异，但在较低频率下，丙酮酸诱导的Sln（OE）EDL的力增强明显更高。SLN过表达并未改变分离的比目鱼肌的抽搐和力-频率曲线。然而，在10分钟的疲劳实验中，Sln（OE）小鼠的EDL和比目鱼肌的疲劳程度均明显低于WT肌肉。有趣的是，Sln（OE）肌肉显示出更高的肉碱棕榈酰转移酶-1蛋白表达，这可以增强脂肪酸代谢。此外，Sln（OE）EDL中的乳酸脱氢酶表达更高，表明糖酵解能力增强。我们还发现，与WT小鼠相比，Sln（OE）分离的短屈肌纤维中的储存-操作性钙内流（SOCE）增加。这些数据使我们得出结论，SLN表达增加通过增加SOCE和肌肉能量代谢来改善长时间肌肉活动期间的骨骼肌性能。
