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辅酶 Q 纳米盘能抵抗他汀类药物对 C2C12 肌管的作用。

Coenzyme Q nanodisks counteract the effect of statins on C2C12 myotubes.

机构信息

Department of Biochemistry and Molecular Biology, University of Nevada, Reno, NV.

Department of Pharmacology, University of Nevada, Reno, NV.

出版信息

Nanomedicine. 2021 Oct;37:102439. doi: 10.1016/j.nano.2021.102439. Epub 2021 Jul 10.

Abstract

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.

摘要

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。

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