HEK 293细胞
石墨烯
活力测定
细胞毒性
谷胱甘肽
细胞生物学
转录组
细胞凋亡
活性氧
生物
化学
生物物理学
分子生物学
生物化学
体外
材料科学
纳米技术
基因表达
基因
酶
作者
Sangiliyandi Gurunathan,Muhammad Arsalan Iqbal,Muhammad Qasim,Chanhyeok Park,Hyunjin Yoo,Jeong Ho Hwang,Sang Jun Uhm,Hyuk Song,Chankyu Park,Jeong Tae,Youngsok Choi,Jin‐Hoi Kim,Kwonho Hong
出处
期刊:Nanomaterials
[MDPI AG]
日期:2019-07-02
卷期号:9 (7): 969-969
被引量:67
摘要
Graphene, a two-dimensional carbon sheet with single-atom thickness, shows immense promise in several nanoscientific and nanotechnological applications, including in sensors, catalysis, and biomedicine. Although several studies have shown the cytotoxicity of graphene oxide in different cell types, there are no comprehensive studies on human embryonic kidney (HEK293) cells that include transcriptomic analysis and an in vitro investigation into the mechanisms of cytotoxicity following exposure to graphene oxide. Therefore, we exposed HEK293 cells to different concentrations of graphene oxide for 24 h and performed several cellular assays. Cell viability and proliferation assays revealed a significant dose-dependent cytotoxic effect on HEK293 cells. Cytotoxicity assays showed increased lactate dehydrogenase (LDH) leakage and reactive oxygen species (ROS) generation, and decreased levels of reduced glutathione (GSH) and increased level of oxidized glutathione indicative of oxidative stress. This detailed mechanistic approach showed that graphene oxide exposure elicits significant decreases in mitochondrial membrane potential and ATP synthesis, as well as in DNA damage and caspase 3 activity. Furthermore, our RNA-Seq analysis revealed that HEK293 cells exposed to graphene oxide significantly altered the expression of genes involved in multiple apoptosis-related biological pathways. Moreover, graphene oxide exposure perturbed the expression of key transcription factors, promoting these apoptosis-related pathways by regulating their downstream genes. Our analysis provides mechanistic insights into how exposure to graphene oxide induces changes in cellular responses and massive cell death in HEK293 cells. To our knowledge, this is the first study describing a combination of cellular responses and transcriptome in HEK293 cells exposed to graphene oxide nanoparticles, providing a foundation for understanding the molecular mechanisms of graphene oxide-induced cytotoxicity and for the development of new therapeutic strategies.
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