Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV.
Department of Pharmacology, University of Nevada, Reno, NV.
Nanomedicine. 2021 Oct;37:102439. doi: 10.1016/j.nano.2021.102439. Epub 2021 Jul 10.
Depletion of coenzyme Q (CoQ) is associated with disease, ranging from myopathy to heart failure. To induce a CoQ deficit, C2C12 myotubes were incubated with high dose simvastatin. This resulted in a concentration-dependent inhibition of cell viability. Simvastatin-induced effects were prevented by co-incubation with mevalonic acid. When myotubes were incubated with 60 μM simvastatin, mitochondrial CoQ content decreased while co-incubation with CoQ nanodisks (ND) increased mitochondrial CoQ levels and improved cell viability. Incubation of myotubes with simvastatin also led to a reduction in oxygen consumption rate (OCR). When myotubes were co-incubated with simvastatin and CoQ ND, the decline in OCR was ameliorated. The data indicate that CoQ ND represent a water soluble vehicle capable of delivering CoQ to cultured myotubes. Thus, these biocompatible nanoparticles have the potential to bypass poor CoQ oral bioavailability as a treatment option for individuals with severe CoQ deficiency syndromes and/or aging-related CoQ depletion.
辅酶 Q(CoQ)的耗竭与疾病有关,范围从肌肉病到心力衰竭。为了诱导 CoQ 缺乏,用高剂量辛伐他汀孵育 C2C12 肌管。这导致细胞活力的浓度依赖性抑制。辛伐他汀诱导的作用可以通过与甲羟戊酸共孵育来预防。当肌管用 60 μM 辛伐他汀孵育时,线粒体 CoQ 含量减少,而与 CoQ 纳米盘(ND)共孵育则增加线粒体 CoQ 水平并提高细胞活力。用辛伐他汀孵育肌管也会导致耗氧量(OCR)降低。当肌管与辛伐他汀和 CoQ ND 共孵育时,OCR 的下降得到改善。数据表明,CoQ ND 代表一种水溶性载体,能够将 CoQ 递送到培养的肌管中。因此,这些生物相容性纳米颗粒有可能绕过 CoQ 的口服生物利用度差,作为治疗严重 CoQ 缺乏综合征和/或与年龄相关的 CoQ 耗竭个体的治疗选择。