The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation.
The effects of silver nanoparticles on mouse embryonic stem cell self-renewal and proliferation.
复制标题
DOI：
10.1016/j.toxrep.2015.05.005
复制
发表时间：
2015
影响因子：
--
通讯作者：
Hong Y
中科院分区：
文献类型：
--
作者：
Rajanahalli P;Stucke CJ;Hong Y
银纳米颗粒（AgNPs）由于其独特的抗菌性能在许多常用的医疗和商业产品中得到迅速普及。银纳米颗粒对干细胞自我更新和增殖的影响的分子机制尚未得到很好的理解。这项工作的目的是使用小鼠胚胎干细胞（mESC）作为细胞模型来评估AgNPs的毒性。mESC是一种非常特殊的细胞类型，具有自我更新和分化特性。本项目的目的是确定具有不同表面化学组成的AgNPs对mESCs的自我更新和细胞周期的影响。两种不同的表面化学成分的银纳米颗粒，多糖涂层和烃涂层，被用来测试其对自我更新和增殖的mESCs的毒性作用。结果表明，多糖包被的和烃包被的AgNPs改变了mESCs的细胞形态。细胞周期分析表明，AgNPs通过抑制视网膜母细胞瘤（Retinoblastoma，Rb）蛋白的过度磷酸化，诱导mESCs细胞周期阻滞于G1期和S期。此外，AgNPs暴露降低了负责mESCs多能性的Oct 4A亚型表达，并诱导了几种亚型OCT 4 B-265、OCT 4 B-190、OCT 4 B-164的表达，这些亚型被认为参与了干细胞应激反应。此外，活性氧（ROS）的生产与两种不同的表面化学成分的银纳米粒子的证据支持我们的假设，即毒性效应银纳米粒子暴露是由于过量的ROS，改变了基因表达和蛋白质修饰。多糖包被减少了活性氧的产生，从而降低了AgNPs的毒性。
Silver nanoparticles (AgNPs) are gaining rapid popularity in many commonly used medical and commercial products for their unique anti-bacterial properties. The molecular mechanisms of effects of AgNPs on stem cell self-renewal and proliferation have not yet been well understood. The aim of the work is to use mouse embryonic stem cells (mESCs) as a cellular model to evaluate the toxicity of AgNPs. mESC is a very special cell type which has self-renewal and differentiation properties. The objective of this project is to determine the effects of AgNPs with different surface chemical compositions on the self-renewal and cell cycle of mESCs. Two different surface chemical compositions of AgNPs, polysaccharide-coated and hydrocarbon-coated, were used to test their toxic effects on self-renewal and proliferation of mESCs. The results indicated that both polysaccharide-coated and hydrocarbon-coated AgNPs changed the cell morphology of mESCs. Cell cycle analysis indicated that AgNPs induced mESCs cell cycle arrest at G1 and S phases through inhibition of the hyperphosphorylation of Retinoblastoma (Rb) protein. Furthermore, AgNPs exposure reduced Oct4A isoform expression which is responsible for the pluripotency of mESCs, and induced the expression of several isoforms OCT4B-265, OCT4B-190, OCT4B-164 which were suggested involved in stem cell stresses responses. In addition, the evidence of reactive oxygen species (ROS) production with two different surface chemical compositions of AgNPs supported our hypothesis that the toxic effect AgNPs exposure is due to overproduction of ROS which altered the gene expression and protein modifications. Polysaccharide coating reduced ROS production, and thus reduced the AgNPs toxicity.