NOX4- and Nrf2-mediated oxidative stress induced by silver nanoparticles in vascular endothelial cells.
Xia SunYi YangJunpeng ShiChengcheng WangZhenfeng YuHongwu ZhangPublished in: Journal of applied toxicology : JAT (2017)
It has been widely reported that silver nanoparticles (AgNPs) induce oxidative stress in various cell lines. However, the mechanism for this effect and its consequences for cellular signaling are poorly understood. In this study, human umbilical vein endothelial cells (HUVECs) were used to assess the toxicity and investigate the associated molecular mechanisms caused by exposure to AgNPs. We demonstrated that AgNP exposure significantly and dose-dependently decreased the cell viability, induced reactive oxygen species (ROS) generation and led to early apoptosis in HUVECs. Our findings showed that AgNPs induced excess ROS production that affected the signaling pathways by a mechanism that depended on activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity through upregulation of NADPH oxidase 4 (NOX4) protein expressions. Moreover, AgNPs could disrupt the inactivation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response, which is considered another important element for oxidative stress caused by AgNPs in HUVECs. The redox imbalance between NOX4 and Nrf2 was an important cause for the ROS overproduction that led to cell injury in HUVECs. The results provided insight into the mechanisms of oxidative stress induced by AgNPs in vascular endothelial cells.
Keyphrases
- silver nanoparticles
- oxidative stress
- reactive oxygen species
- diabetic rats
- endothelial cells
- high glucose
- dna damage
- nuclear factor
- induced apoptosis
- ischemia reperfusion injury
- signaling pathway
- cell death
- toll like receptor
- cell therapy
- poor prognosis
- drug induced
- heat shock
- pi k akt
- single cell
- cell proliferation
- amino acid
- epithelial mesenchymal transition
- small molecule
- binding protein
- immune response
- bone marrow