Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging.
Endogenously determined restriction of food intake overcomes excitation-contraction uncoupling in JP45KO mice with aging.
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DOI：
10.1016/j.exger.2012.01.004
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发表时间：
2012-04
影响因子：
3.9
通讯作者：
Zorzato, Francesco
中科院分区：
文献类型：
--
作者：
Delbono, Osvaldo;Messi, Maria Laura;Wang, Zhong-Min;Treves, Susan;Mosca, Barbara;Bergamelli, Leda;Nishi, Miyuki;Takeshima, Hiroshi;Shi, Hang;Xue, Bingzhong;Zorzato, Francesco
随着年龄的增长，肌肉力量的下降与导致其的总肌肉质量的损失不成比例。敲除JP 45，骨骼肌肌浆网（SR）交界面膜的一种整合蛋白，导致电压门控Ca 2+通道Cav1.1表达减少;兴奋收缩解偶联（ECU）;和肌肉力量的损失。在这里，我们表明雄性JP 45 KO小鼠在12和18个月时Cav1.1表达、电荷运动、SR Ca 2+释放、体外收缩力和持续强迫跑步保持稳定。它们还表现出3-4个月小鼠报告的ECU水平。在以后的年龄没有进一步下降的记录。保留的ECC与在三联体连接处直接或间接与JP 45相互作用的任何蛋白质的表达增加无关。然而，与WT相比，维持的肌肉力量和身体表现与脑中JP 45表达的消融、自发和显著减少的食物摄入以及暴露于高脂肪饮食时肥胖倾向的降低相关。我们提出：（1）内源性食物摄入限制主要通过下调下丘脑弓状核中神经肽Y的表达来克服JP 45消融对ECC和骨骼肌力的有害影响;（2）JP 45 KO小鼠构成了一个宝贵的模型，以研究控制食物摄入的机制以及骨骼肌功能随年龄的增长。
The decline in muscular strength with age is disproportionate to the loss in total muscle mass that causes it. Knocking out JP45, an integral protein of the junctional face membrane of the skeletal muscle sarcoplasmic reticulum (SR), results in decreased expression of the voltage-gated Ca2+ channel, Cav1.1; excitation-contraction uncoupling (ECU); and loss of muscle force. Here, we show that Cav1.1 expression, charge movement, SR Ca2+ release, in vitro contractile force, and sustained forced running remain stable in male JP45KO mice at 12 and 18 months. They also exhibit the level of ECU reported for 3–4-month mice. No further decline at later ages was recorded. Preserved ECC was not related to increased expression of any protein that directly or indirectly interacts with JP45 at the triad junction. However, maintained muscle force and physical performance were associated with ablation of JP45 expression in the brain, spontaneous and significantly diminished food intake and less tendency toward obesity when exposed to a high-fat diet compared to WT. We propose that (1) endogenously generated restriction in food intake overcomes the deleterious effects of JP45 ablation on ECC and skeletal muscle force mainly through downregulation of neuropeptide-Y expression in the hypothalamic arcuate nucleus; and (2) the JP45KO mouse constitutes an invaluable model to examine the mechanisms controlling food intake as well as skeletal muscle function with aging.
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DOI：
10.1007/978-90-481-9713-2_6
发表时间：
2011-01-01
期刊：
SARCOPENIA-AGE-RELATED MUSCLE WASTING AND WEAKNESS: MECHANISMS AND TREATMENTS
影响因子：
--
作者：
Delbono, Osvaldo
通讯作者：
Delbono, Osvaldo
影响因子：
5.5
作者：
Lyfenko, Alla D.;Dirksen, Robert T.
通讯作者：
Dirksen, Robert T.
影响因子：
2.4
作者：
González, E;Messi, ML;Delbono, O
通讯作者：
Delbono, O
DOI：
10.1073/pnas.070056497
发表时间：
2000-04-11
影响因子：
11.1
作者：
González, A;Kirsch, WG;Rios, E
通讯作者：
Rios, E
影响因子：
4.8
作者：
Renganathan, M;Messi, ML;Delbono, O
通讯作者：
Delbono, O