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RISS 인기검색어
- 검색키워드
- 저자 : Sopariwala, Danesh Hooshmand (검색결과 2 건)
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Sarcolipin Overexpression Improves Fatigue Resistance by Enhancing Skeletal Muscle Energetics
Sopariwala, Danesh Hooshmand The Ohio State University ProQuest Dissertations & 2015 해외박사(DDOD)
소속기관이 구독 중이 아닌 경우 오후 4시부터 익일 오전 9시까지 원문보기가 가능합니다.
Sarcolipin (SLN) is a regulator of sarco(endo)plasmic reticulum calcium ATPase (SERCA) in skeletal muscle. Recent studies using SLN knockout ( Sln-/-) mice have identified SLN as a key player in muscle thermogenesis and metabolism. In this study, we exploited a SLN overexpression (SlnOE) mouse model to determine how increased SLN level affected, metabolic rate, exercise capacity/ fatigue in whole animals and isolated muscle, as well as muscle contractile properties and calcium dynamics. We found that SlnOE mice were more resistant to fatigue and ran significantly longer distance than wild type (WT). Studies with isolated extensor digitorum longus (EDL) muscle showed that SlnOE EDL produced higher twitch force than WT. The force-frequency curves were not different between WT and SlnOE EDLs, but at lower frequencies the pyruvate induced potentiation of force had greater significance in Sln OE EDL than WT. SLN overexpression did not alter the twitch and force frequency curve in isolated soleus muscle. However, during a 10 minute fatigue protocol both EDL and soleus from SlnOE mice fatigued significantly less than WT muscles. Although the expression of mitochondrial oxidative phosphorylation enzymes and isolated mitochondrial respiration was not different between WT and SlnOE muscles, the latter showed higher carnitine palmitoyl transferase-1 protein expression, which could enhance fatty acid metabolism. In addition, lactate dehydrogenase expression was higher in SlnOE EDL suggesting increased glycolytic capacity. SLN overexpression resulted in altered myplasmic Ca2+ dynamics as measured in isolated flexor digitorum brevis (FDB) fibers. FDB fibers from SlnOE mice had a significantly longer decay phase of Ca 2+ transient during a single twitch and also showed a significant increase in store operated calcium entry (SOCE) and basal Ca 2+, than WT FDB fibers. Moreover, the levels of key SOCE proteins like stromal interaction molecule 1, transient receptor like ion channel C 3 (TRPC 3) and TRPC 4 were significantly higher in SlnOE FDB fibers than WT. In addition, we showed that inhibition of SOCE caused a greater reduction in force of SlnOE EDL than WT EDL during fatigue. Furthermore, the increased muscle energetics and improved resistance to fatigue of SlnOE mice enabled them to rescue Sln-/- mice from acute cold induced hypothermia. These data allow us to conclude that increased SLN expression improves skeletal muscle and whole animal performance during prolonged physical activity.
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