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Mitochondrial Coenzyme Q10 Delivery Improves Energy Production in Rat Cardiac Myoblasts and Duchenne Muscular Dystrophy Model Rat Cardiomyocytes
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DOI：10.1248/bpb.b25-00327.png)
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Abstract
En 中文
Enhancing cardiomyocyte mitochondrial function has been reported as a potential therapeutic approach for various diseases. However, this is technically difficult, and its practical use has not been described. Although treatments such as exon skipping for skeletal muscle have been established for Duchenne muscular dystrophy (DMD), no curative treatment has been developed for DMD cardiomyopathy, and only cardioprotective medications and symptomatic treatments are available. In this study, we attempted to activate cardiac myocyte mitochondria via direct drug delivery using lipid nanoparticles and investigated the application of this strategy to diseased cells. First, we delivered CoQ10, a mitochondrial activator with cellular antioxidant capacity, into mitochondria in H9C2 cells using MITO-Porter, a mitochondria-directed nanoparticle. Cellular MITO-Porter uptake was measured using flow cytometry. Co-localization of mitochondria and MITO-Porter was confirmed using confocal laser microscopy. Mitochondrial respiratory capacity was measured using an extracellular flux analyzer. Furthermore, the concentration-response relationships of the amount of nanoparticles or CoQ10 with mitochondrial energy production capacity were confirmed. Next, we examined the possibility of improving mitochondrial energy production capacity in diseased cells. Cells were isolated from the myocardium of DMD model rats generated using the CRISPR-Cas9 system. Mitochondrial energy production capacity was lower in DMD primary cardiomyocytes than in wild-type primary cardiomyocytes. CoQ10 delivery to mitochondria in DMD primary cardiomyocytes using MITO-Porter improved mitochondrial energy production capacity. Thus, enhanced cardiomyocyte mitochondrial energy production might represent a potential treatment for cardiomyopathy.
Keywords:
cardiomyocyte
Duchenne muscular dystrophy
drug delivery system
nanoparticle dose dependency
mitochondrial respiratory capacity
CoQ10
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