pH 响应型氧化还原纳米颗粒在帕金森病细胞模型中降低 pH 时保护 SH-SY5Y 细胞。
pH-Responsive Redox Nanoparticles Protect SH-SY5Y Cells at Lowered pH in a Cellular Model of Parkinson's Disease.
机构信息
Laboratory of Analytical Biochemistry, Institute of Food Technology and Nutrition, College of Natural Sciences, Rzeszow University, 4 Zelwerowicza Street, 35-601 Rzeszow, Poland.
Department of Bioenergetics, Food Analysis and Microbiology, Institute of Food Technology and Nutrition, College of Natural Sciences, Rzeszow University, 4 Zelwerowicza Street, 35-601 Rzeszow, Poland.
出版信息
Molecules. 2021 Jan 21;26(3):543. doi: 10.3390/molecules26030543.
The damage to SH-SY5Y cells by 6-hydroxydopamine (6-OHDA) is an established cellular model of Parkinson's disease (PD). Redox nanoparticles are a promising tool for therapy, including neurodegenerative diseases. As pH of the brain tissue at sites affected by PD is lowered down to 6.5, we studied the effect of pH-responsive redox nanoparticles (poly(ethylene glycol)--poly[4-(2,2,6,6-tetramethylpiperidine-1-oxyl)aminomethylstyrene]), which change their structure in a pH-dependent manner and become active below pH 7 (NRNPs ), on the viability of SH-SY5Y cells treated with 6-OHDA at pH 6.5 and 7.4. Pretreatment of the cells with NRNPs (15-75 μM) prior to the 6-OHDA treatment increased their survival in a concentration-dependent manner at pH 6.5, but not at pH 7.4. Among several parameters studied (ATP and GSH content, the level of reactive oxygen species, mitochondrial potential, mitochondrial mass), only the mitochondrial mass was dose-dependently protected by NRNPs at pH 6.5, but not at pH 7.4. These results indicate that the action of NRNPs on mitochondria underlies their protective effect in this cellular model of PD. These results may have potential importance for future applications of NRNPs in preclinical and perhaps clinical studies.
6-羟多巴胺（6-OHDA）对 SH-SY5Y 细胞的损伤是帕金森病（PD）的一种成熟的细胞模型。氧化还原纳米颗粒是一种有前途的治疗工具，包括神经退行性疾病。由于 PD 影响部位的脑组织 pH 值降低至 6.5，我们研究了 pH 响应型氧化还原纳米颗粒（聚（乙二醇）-聚[4-（2,2,6,6-四甲基哌啶-1-氧）氨基甲基苯乙烯]）的作用，这些纳米颗粒的结构在 pH 依赖性方式下发生变化，并且在 pH 值低于 7 时变得活跃（NRNPs），研究了其对在 pH 6.5 和 7.4 下用 6-OHDA 处理的 SH-SY5Y 细胞活力的影响。在 6-OHDA 处理之前，用 NRNPs（15-75 μM）预处理细胞可在 pH 6.5 下以浓度依赖性方式增加细胞存活率，但在 pH 7.4 下则不然。在所研究的几个参数中（ATP 和 GSH 含量、活性氧水平、线粒体电位、线粒体质量），只有线粒体质量在 pH 6.5 下被 NRNPs 剂量依赖性地保护，而在 pH 7.4 下则不然。这些结果表明，NRNPs 对线粒体的作用是其在这种 PD 细胞模型中保护作用的基础。这些结果对于 NRNPs 在临床前和临床研究中的未来应用可能具有重要意义。
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