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Polymer-coated nanoparticles and their effects on mitochondrial function in brain endothelial cells.
Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2019-11-01 , DOI: 10.1016/j.taap.2019.114800
Aniela Bittner 1 , Angélique Dominique Ducray 1 , Michael Hubert Stoffel 2 , Andrea Felser 3 , Meike Mevissen 1
Affiliation  

Laser tissue soldering is a novel treatment method for injuries of hollow organs such as cerebrovascular aneurysms. Nanomaterials contained in the solder are foreign to the body. Hence, it is indispensable to carefully examine possible adverse effects prior to introducing this technique. The aim of this study was to characterize the impact of different concentrations of polymer-coated silica nanoparticles (NPs) on mitochondrial function and integrity of brain endothelial cells using the rat brain capillary endothelial cell line rBCEC4. At maximal capacity, NP exposure resulted in a decrease in the oxygen consumption rate whereas glycolysis was not affected. In combination with a stressor, i.e. lack of glucose in the medium, NP exposure interfered primarily with glycolytic ATP generation rather than oxidative phosphorylation. Furthermore, NPs caused a metabolic shift towards a stressed phenotype, exhibiting increased levels of the oxygen consumption rate and the extracellular acidification rate compared to untreated controls. Overall, mitochondrial mass, distribution and morphology as well as intracellular ATP content were not altered. The mitochondrial membrane potential was increased after exposure to the highest NP concentration and the content of proteins involved in mitochondrial dynamics was changed slightly, indicating possible modifications of the fusion / fission balance. In conclusion, PCL-NP exposure changed mitochondrial respiration, especially under glucose deprivation, but did not affect mitochondrial morphology and distribution. Further studies are needed to investigate whether the functional effects are transient or long-term as this will be crucial for the use of these NPs in laser tissue soldering.

中文翻译:

聚合物包覆的纳米颗粒及其对脑内皮细胞线粒体功能的影响。

激光组织焊接是一种新型的治疗中空器官(如脑血管动脉瘤)损伤的方法。焊料中所含的纳米材料对人体是异物。因此,在引入此技术之前仔细检查可能的不利影响是必不可少的。这项研究的目的是使用大鼠脑毛细血管内皮细胞系rBCEC4表征不同浓度的聚合物包覆的二氧化硅纳米颗粒(NPs)对线粒体功能和脑内皮细胞完整性的影响。在最大容量下,NP暴露导致耗氧率降低,而糖酵解不受影响。与压力源(即培养基中缺少葡萄糖)结合使用时,NP暴露主要干扰糖酵解ATP的产生,而不是氧化磷酸化。此外,NPs导致代谢转变为应激表型,与未处理的对照组相比,表现出更高的耗氧率和细胞外酸化率。总体而言,线粒体质量,分布和形态以及细胞内ATP含量均未改变。暴露于最高的NP浓度后线粒体膜电位增加,并且参与线粒体动力学的蛋白质含量略有变化,表明融合/裂变平衡可能发生改变。总之,PCL-NP暴露改变了线粒体呼吸,特别是在葡萄糖缺乏的情况下,但不影响线粒体的形态和分布。
更新日期:2019-11-01
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