化学纳米疗法：含硝酰自由基的纳米颗粒保护神经母细胞瘤SH-SY5Y细胞免受β-淀粉样蛋白诱导的氧化应激。

Chemical nanotherapy: nitroxyl radical-containing nanoparticle protects neuroblastoma SH-SY5Y cells from Abeta-induced oxidative stress.

作者信息

Chonpathompikunlert Pennapa, Yoshitomi Toru, Han Junkyu, Toh Kazuko, Isoda Hiroko, Nagasaki Yukio

机构信息

Department of Materials Science, Master's School of Medical Sciences, Satellite Laboratory of International Center for Materials Nanoarchitectonics, University of Tsukuba, Tennoudai I-I-I, Tsukuba, Ibaraki 305-8573, Japan.

出版信息

Ther Deliv. 2011 May;2(5):585-97. doi: 10.4155/tde.11.27.

DOI:10.4155/tde.11.27

PMID:22833976

Abstract

BACKGROUND

Excessive accumulation of beta-amyloid (Abeta) has been proposed as a pivotal event in the pathogenesis of Alzheimer's disease. Possible mechanisms underlying Abeta-induced neuronal cytotoxicity include excess production of reactive oxygen species (ROS) and apoptosis. We have designed novel nanoparticles, nitroxyl radical-containing nanoparticles (RNPs), which possess nitroxyl radical in the core and chemically scavenges ROS. This study aimed to determine the potential neuroprotective role of RNPs on Abeta-induced cytotoxicity in human neuroblastoma SH-SY5Y cells.

METHOD

SH-SY5Y cells were preincubated with 0.1-1 mM RNP for 24 h and then incubated with 20 microM Abeta1-42, for 48 h. In every group, cell viability, apoptotic rate, ROS levels including superoxide anion radicals and hydroxyl radicals, ROS production including lipid peroxidation, protein oxidation and DNA oxidation were measured.

RESULTS

SH-SY5Y cells preincubated with 0.1-2 mM RNP for 24 h were protected from Abeta-induced damage. SH-SY5Y cells preincubated with more than 2 mM RNPfor 24 h showed cytotoxicity. From the quantitative analyses, it was observed that RNPs reduced intracellular oxidative stress. RNP treatment significantly reduced the amount of oxidized lipids, proteins and DNA. It also reduced DNA fragmentations, which caused lower apoptosis levels.

CONCLUSION

RNPs are promising intracellular ROS scavengers.

摘要

背景

β-淀粉样蛋白（Aβ）的过度积累被认为是阿尔茨海默病发病机制中的关键事件。Aβ诱导神经元细胞毒性的潜在机制包括活性氧（ROS）的过量产生和细胞凋亡。我们设计了新型纳米颗粒，即含硝酰自由基纳米颗粒（RNP），其核心含有硝酰自由基并能化学清除ROS。本研究旨在确定RNP对人神经母细胞瘤SH-SY5Y细胞中Aβ诱导的细胞毒性的潜在神经保护作用。

方法

将SH-SY5Y细胞与0.1 - 1 mM RNP预孵育24小时，然后与20 μM Aβ1-42孵育48小时。在每组中，测量细胞活力、凋亡率、包括超氧阴离子自由基和羟基自由基在内的ROS水平、包括脂质过氧化、蛋白质氧化和DNA氧化在内的ROS产生情况。

结果

与0.1 - 2 mM RNP预孵育24小时的SH-SY5Y细胞免受Aβ诱导的损伤。与超过2 mM RNP预孵育24小时的SH-SY5Y细胞表现出细胞毒性。从定量分析中观察到，RNP降低了细胞内氧化应激。RNP处理显著减少了氧化脂质、蛋白质和DNA的量。它还减少了DNA片段化，从而导致较低的凋亡水平。