Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway.

Coenzyme Q10 protects astrocytes from ROS-induced damage through inhibition of mitochondria-mediated cell death pathway.
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辅酶 Q10 通过抑制线粒体介导的细胞死亡途径保护星形胶质细胞免受 ROS 诱导的损伤

DOI:
10.7150/ijbs.10174
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发表时间:
2015
影响因子:
9.2
通讯作者:
Li PA
Li PA
中科院分区:
生物学2区
文献类型:
--
作者:
Jing L;He MT;Chang Y;Mehta SL;He QP;Zhang JZ;Li PA

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辅酶Q10(CoQ 10)通过清除活性氧来保护神经细胞免受神经退行性疾病中的氧化应激。本研究旨在研究辅酶Q10是否能够保护星形胶质细胞免受活性氧(ROS)介导的损伤。为此,紫外线B(UVB)照射被用作诱导ROS应激培养星形胶质细胞的工具。将细胞用10和25 μg/ml CoQ 10处理3或24小时,然后将细胞暴露于UVB照射,并在UVB暴露后维持24小时。通过MTT转化测定评估细胞活力。用呼吸计测定线粒体呼吸。虽然超氧化物的产生和线粒体膜电位进行了测量,使用荧光探针,细胞色素C(细胞-C),裂解半胱天冬酶-9,8的水平进行检测,使用蛋白质印迹和/或免疫细胞化学。结果表明,UVB照射降低了细胞活力,这种损伤作用与超氧阴离子积累、线粒体膜电位超极化、线粒体呼吸抑制、细胞内C释放以及caspase-9和caspase-8的激活有关。在UVB暴露前24小时开始用两种不同浓度的CoQ 10处理显著增加了细胞活力。辅酶Q10的保护作用与减少超氧化物、使线粒体膜电位正常化、改善线粒体呼吸、抑制cyto-c释放、抑制caspase-9有关。此外,辅酶Q10增强线粒体生物合成。结论:辅酶Q10可能通过抑制氧化应激、预防线粒体功能障碍、阻断线粒体介导的细胞死亡途径和增强线粒体生物合成来保护星形胶质细胞。
Coenzyme Q10 (CoQ10) acts by scavenging reactive oxygen species to protect neuronal cells against oxidative stress in neurodegenerative diseases. The present study was designed to examine whether CoQ10 was capable of protecting astrocytes from reactive oxygen species (ROS) mediated damage. For this purpose, ultraviolet B (UVB) irradiation was used as a tool to induce ROS stress to cultured astrocytes. The cells were treated with 10 and 25 μg/ml of CoQ10 for 3 or 24 h prior to the cells being exposed to UVB irradiation and maintained for 24 h post UVB exposure. Cell viability was assessed by MTT conversion assay. Mitochondrial respiration was assessed by respirometer. While superoxide production and mitochondrial membrane potential were measured using fluorescent probes, levels of cytochrome C (cyto-c), cleaved caspase-9, and caspase-8 were detected using Western blotting and/or immunocytochemistry. The results showed that UVB irradiation decreased cell viability and this damaging effect was associated with superoxide accumulation, mitochondrial membrane potential hyperpolarization, mitochondrial respiration suppression, cyto-c release, and the activation of both caspase-9 and -8. Treatment with CoQ10 at two different concentrations started 24 h before UVB exposure significantly increased the cell viability. The protective effect of CoQ10 was associated with reduction in superoxide, normalization of mitochondrial membrane potential, improvement of mitochondrial respiration, inhibition of cyto-c release, suppression of caspase-9. Furthermore, CoQ10 enhanced mitochondrial biogenesis. It is concluded that CoQ10 may protect astrocytes through suppression of oxidative stress, prevention of mitochondrial dysfunction, blockade of mitochondria-mediated cell death pathway, and enhancement of mitochondrial biogenesis.
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