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ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines.

ABSTRACT: Zinc oxide (ZnO) quantum dot (QD) is a promising inexpensive inorganic nanomaterials, of which potential toxic effects on biological systems and human health should be evaluated before biomedical application. In this study, the cytotoxicity of ZnO QDs was assessed using HeLa cervical cancer cell and HEK-293T human embryonic kidney cell lines. Cell viability was significantly decreased by treatment with 50 µg/ml ZnO QDs after only 6 h, and the cytotoxicity of ZnO QDs was higher in HEK-293T than in HeLa cells. ZnO QDs increased the level of reactive oxygen species and decreased the mitochondria membrane potential in a dose-dependent manner. Several gene expression involved in apoptosis was regulated by ZnO QDs, including bcl-2 gene and caspase. In HeLa cells, ZnO QDs significantly increased early and late apoptosis, but only late apoptosis was affected in HEK-293T cells. These findings will be helpful for future research and application of ZnO QDs in biomedicine.

SUBMITTER: Yang Y

PROVIDER: S-EPMC7057716 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines.

Yang Yanjie Y Song Zhenhua Z Wu Weixia W Xu Ao A Lv Shuangyu S Ji Shaoping S

Frontiers in pharmacology 20200227

Zinc oxide (ZnO) quantum dot (QD) is a promising inexpensive inorganic nanomaterials, of which potential toxic effects on biological systems and human health should be evaluated before biomedical application. In this study, the cytotoxicity of ZnO QDs was assessed using HeLa cervical cancer cell and HEK-293T human embryonic kidney cell lines. Cell viability was significantly decreased by treatment with 50 µg/ml ZnO QDs after only 6 h, and the cytotoxicity of ZnO QDs was higher in HEK-293T than i ...[more]

PMID: 32180717

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Project description:Leucine-rich repeat kinase 2 (LRRK2) has been linked to dopaminergic neuronal vulnerability to oxidative stress (OS), mitochondrial impairment, and increased cell death in idiopathic and familial Parkinson's disease (PD). However, how exactly this kinase participates in the OS-mitochondria-apoptosis connection is still unknown. We used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 LRRK2 knockout (KO) in the human embryonic kidney cell line 293 (HEK-293) to evaluate the cellular response to the mitochondrial inhibitor complex I rotenone (ROT), a well-known OS and cell death inducer. We report successful knockout of the LRRK2 gene in HEK-293 cells using CRISPR editing (ICE, approximately 60%) and flow cytometry (81%) analyses. We found that HEK-293 LRRK2 WT cells exposed to rotenone (ROT, 50 μM) resulted in a significant increase in intracellular reactive oxygen species (ROS, +7400%); oxidized DJ-1-Cys106-SO3 (+52%); phosphorylation of LRRK2 (+70%) and c-JUN (+171%); enhanced expression of tumor protein (TP53, +2000%), p53 upregulated modulator of apoptosis (PUMA, +1950%), and Parkin (PRKN, +22%); activation of caspase 3 (CASP3, +8000%), DNA fragmentation (+35%) and decreased mitochondrial membrane potential (ΔΨm, -58%) and PTEN induced putative kinase 1 (PINK1, -49%) when compared to untreated cells. The translocation of the cytoplasmic fission protein dynamin-related Protein 1 (DRP1) to mitochondria was also observed by colocalization with translocase of the outer membrane 20 (TOM20). Outstandingly, HEK-293 LRRK2 KO cells treated with ROT showed unaltered OS and apoptosis markers. We conclude that loss of LRRK2 causes HEK-293 to be resistant to ROT-induced OS, mitochondrial damage, and apoptosis in vitro. Our data support the hypothesis that LRRK2 acts as a proapoptotic kinase by regulating mitochondrial proteins (e.g., PRKN, PINK1, DRP1, and PUMA), transcription factors (e.g., c-JUN and TP53), and CASP3 in cells under stress conditions. Taken together, these observations suggest that LRRK2 is an important kinase in the pathogenesis of PD.

Project description:BackgroundGraphene quantum dots (GQDs) provide a bright prospect in the biomedical application because they contain low-toxic compounds and promise imaging of deep tissues and tiny vascular structures. However, the biosafety of this novel QDs has not been thoroughly evaluated, especially in the central nervous system (CNS). The microarray analysis provides a hint that nitrogen-doped GQDs (N-GQDs) exposure could cause ferroptosis in microglia, which is a novel form of cell death dependent on iron overload and lipid peroxidation.ResultsThe cytosolic iron overload, glutathione (GSH) depletion, excessive reactive oxygen species (ROS) production and lipid peroxidation (LPO) were observed in microglial BV2 cells treated with N-GQDs, which indicated that N-GQDs could damage the iron metabolism and redox balance in microglia. The pre-treatments of a specific ferroptosis inhibitor Ferrostatin-1 (Fer-1) and an iron chelater Deferoxamine mesylate (DFO) not only inhibited cell death, but also alleviated iron overload, LPO and alternations in ferroptosis biomarkers in microglia, which were caused by N-GQDs. When assessing the potential mechanisms of N-GQDs causing ferroptosis in microglia, we found that the iron content, ROS generation and LPO level in mitochondria of BV2 cells all enhanced after N-GQDs exposure. When the antioxidant ability of mitochondria was increased by the pre-treatment of a mitochondria targeted ROS scavenger MitoTEMPO, the ferroptotic biological changes were effectively reversed in BV2 cells treated with N-GQDs, which indicated that the N-GQDs-induced ferroptosis in microglia could be attributed to the mitochondrial oxidative stress. Additionally, amino functionalized GQDs (A-GQDs) elicited milder redox imbalance in mitochondria and resulted in less ferroptotic effects than N-GQDs in microglia, which suggested a slight protection of amino group functionalization in GQDs causing ferroptosis.ConclusionN-GQDs exposure caused ferroptosis in microglia via inducing mitochondrial oxidative stress, and the ferroptotic effects induced by A-GQDs were milder than N-GQDs when the exposure method is same. This study will not only provide new insights in the GQDs-induced cell damage performed in multiple types of cell death, but also in the influence of chemical modification on the toxicity of GQDs.

Dataset Information

ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines.

Publications

ZnO Quantum Dots Induced Oxidative Stress and Apoptosis in HeLa and HEK-293T Cell Lines.

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