Dubinin Mikhail V, Stepanova Anastasia E, Igoshkina Anastasia D, Mikheeva Irina B, Talanov Eugeny Yu, Cherepanova Alena A, Belosludtsev Konstantin N
Department of Biochemistry, Cell Biology and Microbiology, Mari State University, 424001 Yoshkar-Ola, Russia.
Laboratory of Experimental Neurobiology, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290 Pushchino, Russia.
Front Biosci (Landmark Ed). 2024 Dec 25;29(12):428. doi: 10.31083/j.fbl2912428.
Ca overload of muscle fibers is one of the factors that secondarily aggravate the development of Duchenne muscular dystrophy (DMD). The purpose of this study is to evaluate the effects of the Ca channel modulator 2-aminoethoxydiphenyl borate (APB) on skeletal muscle pathology in dystrophin-deficient mice.
Mice were randomly divided into six groups: wild type (WT), WT+3 mg/kg APB, WT+10 mg/kg APB, , +3 mg/kg APB, +10 mg/kg APB. APB was administered intraperitoneally daily for 28 days. Finally, we assessed the grip strength and hanging time of mice, the histology and ultrastructure of the quadriceps, as well as the parameters reflecting quadricep mitochondrial function.
3 mg/kg APB was shown to reduce creatine kinase activity in the serum, intensity of degeneration and the level of fibrosis in the quadriceps of mice, and improved tissue ultrastructure. However, this effect of APB was not sufficient to improve grip strength and hanging time of mice. The effect of 3 mg/kg APB may be due to improve Ca homeostasis in skeletal muscles, as evidenced by a trend toward decreased Ca overload of quadricep mitochondria. High dose of APB (10 mg/kg body weight) showed less pronounced effect on the pathological phenotype of mice. Moreover, 10 mg/kg APB disrupted the ultrastructure of the quadriceps and caused a decrease in grip strength in WT mice.
APB is able to improve the phenotype in mouse DMD model. However, the effect of APB is quite limited, which may be due to its multitargeting of Ca channels in the membranes of muscle fibers and intracellular organelles, differentially expressed in DMD.
肌纤维钙超载是继发性加重杜氏肌营养不良症（DMD）发展的因素之一。本研究旨在评估钙通道调节剂2-氨基乙氧基二苯硼酸（APB）对肌营养不良蛋白缺陷小鼠骨骼肌病理的影响。
将小鼠随机分为六组：野生型（WT）、WT + 3 mg/kg APB、WT + 10 mg/kg APB、[此处原文缺失组名] + 3 mg/kg APB、[此处原文缺失组名] + 10 mg/kg APB。每天腹腔注射APB，持续28天。最后，我们评估了小鼠的握力和悬挂时间、股四头肌的组织学和超微结构，以及反映股四头肌线粒体功能的参数。
结果显示，3 mg/kg APB可降低[此处原文缺失组名]小鼠血清中的肌酸激酶活性、股四头肌的变性强度和纤维化水平，并改善组织超微结构。然而，APB的这种作用不足以改善[此处原文缺失组名]小鼠的握力和悬挂时间。3 mg/kg APB的作用可能是由于改善了骨骼肌中的钙稳态，股四头肌线粒体钙超载有下降趋势证明了这一点。高剂量的APB（10 mg/kg体重）对[此处原文缺失组名]小鼠的病理表型影响较小。此外，10 mg/kg APB破坏了WT小鼠股四头肌的超微结构，并导致其握力下降。
APB能够改善[此处原文缺失组名]小鼠DMD模型的表型。然而，APB的作用相当有限，这可能是由于其对肌纤维膜和细胞内细胞器中钙通道的多靶点作用，这些钙通道在DMD中差异表达。
