Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy
Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy
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DOI：
10.1152/japplphysiol.00803.2009
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Reggiani, Carlo
中科院分区：
文献类型：
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作者：
Blaauw, Bert;Agatea, Lisa;Reggiani, Carlo
Blaauw B、Agatea L、Toniolo L、Canato M、Quarta M、Dyar KA、Danieli-Betto D、Betto R、Schiaffino S、Reggiani C。偏心收缩导致肌营养不良症中的肌原纤维功能障碍。 J Appl Physiol 108: 105-111, 2010。首次发表于 2009 年 11 月 12 日； doi:10.1152/japplphyol.00803.2009.-人们普遍认为，肌养蛋白缺陷型 mdx 小鼠的骨骼肌比野生型小鼠的骨骼肌更容易受到偏心收缩造成的损伤。然而，这种增强的力下降所涉及的下游机制仍然存在争议。我们研究了野生型小鼠和三种不同的肌肉营养不良模型：mdx、α-肌聚糖 (Sgca) 缺失和胶原 6A1 (Col6a1) 缺失小鼠体内离心收缩引起的收缩力的降低。在 mdx 和 Sgcannull 小鼠中，力下降了 35%，而野生型小鼠则下降了 14%。 Col6a1 缺失小鼠的力下降与野生型小鼠相当。为了确定力下降的决定因素，我们测量了从体内暴露于偏心收缩的腓肠肌和对侧未刺激肌肉解剖的透化纤维中产生的力。在 mdx 和 Sgca-null 小鼠的纤维中，可检测到体内偏心收缩后带皮纤维的力损失，但在野生型和 Col6a1-null 小鼠的纤维中未检测到。仅当在体内引发偏心收缩时，才观察到 mdx 和 Sgca-null 小鼠的力减少增强，因为体外引发的偏心收缩对野生型和营养不良的皮肤纤维具有相同的效果。这些结果表明：1）增强的力损失是由于所有纤维中存在的肌原纤维损伤，而不是单个纤维变性，2）导致增强的力减少的机制在体内活跃，并在纤维透化后损失。
Blaauw B, Agatea L, Toniolo L, Canato M, Quarta M, Dyar KA, Danieli-Betto D, Betto R, Schiaffino S, Reggiani C. Eccentric contractions lead to myofibrillar dysfunction in muscular dystrophy. J Appl Physiol 108: 105-111, 2010. First published November 12, 2009; doi:10.1152/japplphysiol.00803.2009.-It is commonly accepted that skeletal muscles from dystrophin-deficient mdx mice are more susceptible than those from wild-type mice to damage from eccentric contractions. However, the downstream mechanisms involved in this enhanced force drop remain controversial. We studied the reduction of contractile force induced by eccentric contractions elicited in vivo in the gastrocnemius muscle of wild-type mice and three distinct models of muscle dystrophy: mdx, alpha-sarcoglycan (Sgca)-null, and collagen 6A1 (Col6a1)-null mice. In mdx and Sgcanull mice, force decreased 35% compared with 14% in wild-type mice. Drop of force in Col6a1-null mice was comparable to that in wild-type mice. To identify the determinants of the force drop, we measured force generation in permeabilized fibers dissected from gastrocnemius muscle that had been exposed in vivo to eccentric contractions and from the contralateral unstimulated muscle. A force loss in skinned fibers after in vivo eccentric contractions was detectable in fibers from mdx and Sgca-null, but not wild-type and Col6a1-null, mice. The enhanced force reduction in mdx and Sgca-null mice was observed only when eccentric contractions were elicited in vivo, since eccentric contractions elicited in vitro had identical effects in wild-type and dystrophic skinned fibers. These results suggest that 1) the enhanced force loss is due to a myofibrillar impairment that is present in all fibers, and not to individual fiber degeneration, and 2) the mechanism causing the enhanced force reduction is active in vivo and is lost after fiber permeabilization.