High-throughput transcriptomics: An insight on the pathways affected in HepG2 cells exposed to nickel oxide nanoparticles. (April 2020)

• Record Type: Journal Article
• Authors: Saquib, Quaiser; Xia, Pu; Siddiqui, Maqsood A.; Zhang, Junjiang; Xie, Yuwei; Faisal, Mohammad; Ansari, Sabiha M.; Alwathnani, Hend A.; Alatar, Abdulrahman A.; Al-Khedhairy, Abdulaziz A.; Zhang, Xiaowei
• Is Part Of: Chemosphere. Volume 244(2020)
• Publication Date: 2020-04
• Subjects: NiO-NPs -- RNA-Seq -- Toxicogenomics -- Apoptosis -- Transcriptome -- Nanoparticles; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2019.125488
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Nickel oxide nanoparticles (NiO-NPs) have been used in several consumer goods, reported to demonstrate the hepatotoxic effects in vitro and in vivo test models. Nonetheless the molecular mechanism of hepatotoxicity is still missing. Hence, a toxicogenomic approach integrating microscopic techniques and high-throughput RNA sequencing (RNA-Seq) was applied to reveal hepatotoxicity in human hepatocellular carcinoma cells (HepG2). NiO-NPs induced a concentration dependent (5–100 μg/ml) cytotoxicity, with a No observed effect level (NOEL) of 5 μg/ml. Hypoxia-inducible transcription factor-1α ( HIF-1α ) and miR-210 microRNA were upregulated at 25 and 100 μg/ml, while significant alteration on transcriptome at mRNA and pathway level was observed at non-toxic level of NiO-NPs treatment. The treated cells also showed activation of glycolysis, glutathione, lysosomes and autophagy pathways by a pathway-driven analysis. Flow cytometric analysis affirmed the elevation in nitric oxide (NO), Ca ++ influx, esterase, and disruption of mitochondrial membrane potential ( ΔΨm ). Cell cycle dysregulation was affirmed by the appearance of 30.5% subG1 apoptotic peak in NiO-NPs (100 μg/ml) treated cells. The molecular responses were consistent with the microscopic observation that NiO-NPs induced subcellular alterations in HepG2 cells. We conclude that hypoxia stress played a pivotal role in NiO-NPs induced hepatoxicity in HepG2 cells. Concentration dependent effects on transcriptomics specify a powerful tool to evaluate the molecular mechanisms of nanoparticle induced cytotoxicity. Overall our study unequivocally affirmed the transcriptomic alterations in human cells, consequently the prevalent usage of NiO-NPs should be given subtle consideration owing to its effects on biological processes. Highlights: First report on transcriptome alterations in HepG2 by NiO-NPs exposure. NiO-NPs triggered hypoxia by up-regulation of HIF-1α and miR-210 in HepG2. NiO-NPs toxicity increased Ca ++ influx, NO and ΔΨm in HepG2. NiO-NPs activated p53, p21, p16, MAPKPK2 proteins to induce cell death in HepG2.