Skeletal muscle single fiber force production declines early in juvenile male mice with chronic kidney disease.
Skeletal muscle single fiber force production declines early in juvenile male mice with chronic kidney disease.
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DOI：
10.14814/phy2.15651
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发表时间：
2023-04
影响因子：
2.5
通讯作者：
中科院分区：
文献类型：
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患有慢性肾脏疾病（CKD）的儿童经常表现出身体发育延迟和身体表现下降，可能是由于骨骼肌功能障碍。然而，青少年CKD骨骼肌损伤的细胞和分子基础仍然知之甚少。在幼年雄性（6周龄）CKD和对照小鼠的缓慢（比目鱼肌）和快速（趾长伸肌）收缩肌肉中离体检查细胞（单纤维）和分子（肌球蛋白-肌动蛋白相互作用和肌丝特性）功能。从3周龄开始，通过0.2%腺嘌呤饮食诱导CKD 3周。在患有CKD的幼年雄性小鼠中，较大的肌球蛋白重链（MHC）I和IIA纤维以及所有IIB纤维中的比张力（最大等长力除以横截面积）降低，这是由于肌球蛋白-肌动蛋白交叉桥的强烈结合较少。与对照组相比，幼年CKD小鼠中MHC I和IIB纤维的纤维横截面积不变，而MHC IIA纤维的横截面积增加。CKD减缓了MHC IIA纤维中的跨桥动力学（肌球蛋白力产生速率较慢，肌球蛋白附着时间较长，t on），并加速了MHC IIB纤维中的动力学（t on较短），这可能表明幼年CKD中收缩速度的纤维类型依赖性变化。总体而言，我们的研究结果表明，单纤维肌病是青少年CKD的早期事件，在细胞萎缩发展之前表现为由于较少的强结合肌球蛋白头导致的力产生减少。这些结果值得临床转化，并呼吁早期干预以保护CKD儿童的身体功能。患有早期CKD的幼年小鼠显示单纤维收缩功能降低。细胞力的产生较低，主要是由于结合较弱的肌球蛋白-肌动蛋白交叉桥。此外，肌球蛋白-肌动蛋白跨桥动力学在肌球蛋白重链IIA纤维中减慢。
Children with chronic kidney disease (CKD) frequently exhibit delayed physical development and reduced physical performance, presumably due to skeletal muscle dysfunction. However, the cellular and molecular basis of skeletal muscle impairment in juvenile CKD remains poorly understood. Cellular (single fiber) and molecular (myosin‐actin interactions and myofilament properties) function was examined ex vivo in slow (soleus) and fast (extensor digitorum longus) contracting muscles of juvenile male (6 weeks old) CKD and control mice. CKD was induced by 0.2% adenine diet for 3 weeks starting at 3 weeks of age. Specific tension (maximal isometric force divided by cross‐sectional area) was reduced in larger myosin heavy chain (MHC) I and IIA fibers and in all IIB fibers in juvenile male mice with CKD due to fewer strongly bound myosin‐actin cross‐bridges. Fiber cross‐sectional area in juvenile CKD mice was unchanged in MHC I and IIB fibers and increased in MHC IIA fibers, compared to controls. CKD slowed cross‐bridge kinetics (slower rate of myosin force production and longer myosin attachment time, t on) in MHC IIA fibers, and accelerated kinetics (shorter t on) in MHC IIB fibers, which may indicate fiber type dependent shifts in contractile velocity in juvenile CKD. Overall, our findings show that single fiber myopathy is an early event during juvenile CKD, manifesting prior to the development of cellular atrophy as reduced force generation due to fewer strongly bound myosin heads. These results warrant clinical translation and call for early interventions to preserve physical function in children with CKD. Juvenile mice with early‐stage CKD display reduced single fiber contractile function. Cellular force production is lower primarily due to less strongly bound myosin‐actin cross‐bridges. Additionally, myosin‐actin cross‐bridge kinetics slow in myosin heavy chain IIA fibers.
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DOI：
10.1002/jcsm.12314
发表时间：
2018-10
期刊：
Journal of cachexia, sarcopenia and muscle
影响因子：
--
作者：
Dziegala M;Josiak K;Kasztura M;Kobak K;von Haehling S;Banasiak W;Anker SD;Ponikowski P;Jankowska E
通讯作者：
Jankowska E
影响因子：
41.5
作者：
Kooman, Jeroen P.;Kotanko, Peter;Stenvinkel, Peter
通讯作者：
Stenvinkel, Peter
影响因子：
8
作者：
Gerson, Arlene C.;Wentz, Alicia;Furth, Susan L.
通讯作者：
Furth, Susan L.
影响因子：
3.7
作者：
Fenwick AJ;Wood AM;Tanner BCW
通讯作者：
Tanner BCW
DOI：
10.1152/ajpregu.90564.2008
发表时间：
2008-11-01
影响因子：
2.8
作者：
Luden, Nicholas;Minchev, Kiril;Trappe, Scott
通讯作者：
Trappe, Scott