Effect of the Non-Immunosuppressive MPT Pore Inhibitor Alisporivir on the Functioning of Heart Mitochondria in Dystrophin-Deficient mdx Mice.
Effect of the Non-Immunosuppressive MPT Pore Inhibitor Alisporivir on the Functioning of Heart Mitochondria in Dystrophin-Deficient mdx Mice.
复制标题
非免疫抑制MPT MPT孔抑制剂Alisporivir对肌营养不良蛋白缺陷型MDX小鼠的心脏线粒体功能的影响。
DOI：
10.3390/biomedicines9091232
复制
发表时间：
2021-09-16
期刊：
影响因子：
4.7
通讯作者：
Belosludtsev KN
中科院分区：
文献类型：
--
作者：
Dubinin MV;Starinets VS;Talanov EY;Mikheeva IB;Belosludtseva NV;Serov DA;Tenkov KS;Belosludtseva EV;Belosludtsev KN
支持线粒体功能是改善Duchenne肌营养不良症(DMD)患者骨骼肌功能的治疗策略之一。在这项工作中，我们研究了线粒体通透性转换孔(MPTP)的非免疫抑制抑制剂阿利斯匹韦(5 mg/kg/d)对dystrophin缺陷mdx小鼠心脏表型的影响，该药可减轻骨骼肌坏死过程和炎症的强度。我们发现mdx小鼠心脏线粒体氧化磷酸化强度增加，细胞器对MPT孔道开放的抵抗力增强。Alisporivir对mdx小鼠心脏线粒体功能亢进无明显影响，野生型动物心脏线粒体状态不影响细胞器动力学，但显著抑制线粒体生物发生，减少心肌mtDNA含量。此外，阿利斯匹韦抑制了野生型小鼠心脏线粒体的生物发生。阿利斯波利韦治疗导致MDX小鼠心脏重量减轻，这与心脏内兴奋传递的显著改变有关。后者在用阿利斯匹韦治疗的WT小鼠中也被注意到。本文就阿利斯匹韦用于纠正DMD心脏线粒体功能的前景进行了讨论。
Supporting mitochondrial function is one of the therapeutic strategies that improve the functioning of skeletal muscle in Duchenne muscular dystrophy (DMD). In this work, we studied the effect of a non-immunosuppressive inhibitor of mitochondrial permeability transition pore (MPTP) alisporivir (5 mg/kg/day), reducing the intensity of the necrotic process and inflammation in skeletal muscles on the cardiac phenotype of dystrophin-deficient mdx mice. We found that the heart mitochondria of mdx mice show an increase in the intensity of oxidative phosphorylation and an increase in the resistance of organelles to the MPT pore opening. Alisporivir had no significant effect on the hyperfunctionalization of the heart mitochondria of mdx mice, and the state of the heart mitochondria of wild-type animals did not affect the dynamics of organelles but significantly suppressed mitochondrial biogenesis and reduced the amount of mtDNA in the heart muscle. Moreover, alisporivir suppressed mitochondrial biogenesis in the heart of wild-type mice. Alisporivir treatment resulted in a decrease in heart weight in mdx mice, which was associated with a significant modification of the transmission of excitation in the heart. The latter was also noted in the case of WT mice treated with alisporivir. The paper discusses the prospects for using alisporivir to correct the function of heart mitochondria in DMD.
登录
查看更多内容
影响因子：
--
作者：
Quiros PM;Goyal A;Jha P;Auwerx J
通讯作者：
Auwerx J
影响因子：
3.7
作者：
Pant, Meghna;Sopariwala, Danesh H.;Periasamy, Muthu
通讯作者：
Periasamy, Muthu
DOI：
10.1016/j.bbrc.2018.01.113
发表时间：
2018-02-12
影响因子：
3.1
作者：
Qi, Rui;Wang, Dongtao;Wu, Zhongjun
通讯作者：
Wu, Zhongjun
影响因子：
2.2
作者：
Astashev, M. E.;Serov, D. A.;Tankanag, A., V
通讯作者：
Tankanag, A., V
影响因子：
4
作者：
De Mario, Agnese;Gherardi, Gaia;Mammucari, Cristina
通讯作者：
Mammucari, Cristina