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血小板衍生生长因子-BB可保护T98G细胞中的线粒体免受鱼藤酮的损伤。

PDGF-BB protects mitochondria from rotenone in T98G cells.

作者信息

Cabezas Ricardo, Avila Marcos Fidel, González Janneth, El-Bachá Ramon Santos, Barreto George E

机构信息

Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá, D.C., Colombia.

出版信息

Neurotox Res. 2015 May;27(4):355-67. doi: 10.1007/s12640-014-9509-5. Epub 2014 Dec 17.

Abstract

Rotenone is one of the most-studied neurotoxic substances as it induces oxidative stress processes both in cellular and animal models. Rotenone affects ATP generation, reactive oxygen species (ROS) production, and mitochondrial membrane potential in neurons and astrocyte-like cells. Previous epidemiologic studies have supported the role of neurotrophic factors such as BDNF and GDNF in neuroprotection mainly in neurons; however, only very few studies have focused on the importance of astrocytic protection in neurodegenerative models. In the present study, we assessed the neuroprotective effects of PDGF-BB against toxicity induced by rotenone in the astrocytic-like model of T98G human glioblastoma cell line. Our results demonstrated that pretreatment with PDGF-BB for 24 h increased cell viability, preserved nuclear morphology and mitochondrial membrane potential following stimulation with rotenone, and reduced ROS production nearly to control conditions. These observations were accompanied by important morphological changes induced by rotenone and that PDGF-BB was able to preserve cellular morphology under this toxic stimuli. These findings indicated that PDGF-BB protects mitochondrial functions, and may serve as a potential therapeutic strategy in rotenone-induced oxidative damage in astrocytes.

摘要

鱼藤酮是研究最多的神经毒性物质之一,因为它在细胞和动物模型中都会诱导氧化应激过程。鱼藤酮会影响神经元和星形胶质样细胞中的ATP生成、活性氧(ROS)产生以及线粒体膜电位。先前的流行病学研究支持神经营养因子如脑源性神经营因子(BDNF)和胶质细胞源性神经营因子(GDNF)在神经保护中的作用,主要是在神经元中;然而,只有极少数研究关注星形胶质细胞保护在神经退行性模型中的重要性。在本研究中,我们评估了血小板衍生生长因子BB(PDGF-BB)对鱼藤酮诱导的T98G人胶质母细胞瘤细胞系星形胶质样模型毒性的神经保护作用。我们的结果表明,用PDGF-BB预处理24小时可提高细胞活力,在鱼藤酮刺激后保持核形态和线粒体膜电位,并将ROS产生降低至接近对照条件。这些观察结果伴随着鱼藤酮诱导的重要形态学变化,并且PDGF-BB能够在这种毒性刺激下保持细胞形态。这些发现表明,PDGF-BB可保护线粒体功能,并可能作为一种潜在的治疗策略用于治疗鱼藤酮诱导的星形胶质细胞氧化损伤。

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