The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy.
The Effect of Deflazacort Treatment on the Functioning of Skeletal Muscle Mitochondria in Duchenne Muscular Dystrophy.
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DOI：
10.3390/ijms21228763
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发表时间：
2020-11-19
影响因子：
5.6
通讯作者：
Belosludtsev KN
中科院分区：
文献类型：
--
作者：
Dubinin MV;Talanov EY;Tenkov KS;Starinets VS;Belosludtseva NV;Belosludtsev KN
杜氏肌营养不良症（DMD）是一种严重的遗传性疾病，由于缺乏肌营养不良蛋白，肌细胞完整性所必需的蛋白质。据报道，线粒体功能障碍是DMD的原因。本研究检测了糖皮质激素地夫可特对肌营养不良蛋白缺陷mdx小鼠和WT动物的睾丸肌线粒体功能的影响。由于ETC复合物（复合物III和IV以及ATP合酶）水平的增加，发现地夫唑科特给药可改善mdx小鼠的线粒体呼吸，这可能有助于mdx动物骨骼肌中ATP水平的正常化。Deflazacort治疗改善了mdx小鼠骨骼肌线粒体中的Ca2+单向转运率，可能是通过影响细胞器钙单向转运体的亚基组成。同时，发现地夫可特降低骨骼线粒体对MPT孔开放的阻力，这可能与ANT2和CypD水平的变化有关。在这种情况下，地夫可特也影响了WT小鼠的线粒体。本文讨论了地夫可特对线粒体功能的影响及其改善mdx小鼠肌肉功能的机制。
Duchenne muscular dystrophy (DMD) is a severe hereditary disease caused by a lack of dystrophin, a protein essential for myocyte integrity. Mitochondrial dysfunction is reportedly responsible for DMD. This study examines the effect of glucocorticoid deflazacort on the functioning of the skeletal-muscle mitochondria of dystrophin-deficient mdx mice and WT animals. Deflazacort administration was found to improve mitochondrial respiration of mdx mice due to an increase in the level of ETC complexes (complexes III and IV and ATP synthase), which may contribute to the normalization of ATP levels in the skeletal muscle of mdx animals. Deflazacort treatment improved the rate of Ca2+ uniport in the skeletal muscle mitochondria of mdx mice, presumably by affecting the subunit composition of the calcium uniporter of organelles. At the same time, deflazacort was found to reduce the resistance of skeletal mitochondria to MPT pore opening, which may be associated with a change in the level of ANT2 and CypD. In this case, deflazacort also affected the mitochondria of WT mice. The paper discusses the mechanisms underlying the effect of deflazacort on the functioning of mitochondria and contributing to the improvement of the muscular function of mdx mice.
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DOI：
10.1016/j.bbamcr.2017.01.015
发表时间：
2017-06
期刊：
Biochimica et biophysica acta. Molecular cell research
影响因子：
--
作者：
Bhosale G;Sharpe JA;Koh A;Kouli A;Szabadkai G;Duchen MR
通讯作者：
Duchen MR
影响因子：
6
作者：
Belosludtsev, Konstantin N.;Talanov, Eugeny Yu;Belosludtseva, Natalia, V
通讯作者：
Belosludtseva, Natalia, V
影响因子：
14.8
作者：
Frezza, Christian;Cipolat, Sara;Scorrano, Luca
通讯作者：
Scorrano, Luca
影响因子：
9.9
作者：
Griggs, Robert C.;Miller, J. Phillip;Meyer, James M.
通讯作者：
Meyer, James M.
影响因子：
30.8
作者：
Graham, BH;Waymire, KG;Wallace, DC
通讯作者：
Wallace, DC