ArticleToxicological sciences : an official journal of the Society of Toxicology2010
A system-based comparison of gene expression reveals alterations in oxidative stress, disruption of ubiquitin-proteasome system and altered cell cycle regulation after exposure to cadmium and methylmercury in mouse embryonic fibroblast.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Heavy metal-induced disruption of the autophagy-lysosomal pathway: implications for aging and neurodegenerative disorders.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Review
- Methylmercury Induces Apoptosis in Mouse C17.2 Neural Stem Cells through the Induction of OSGIN1 Expression by NRF2.International journal of molecular sciences · 2024Article
- Multifunctional Metallothioneins as a Target for Neuroprotection in Parkinson's Disease.Antioxidants (Basel, Switzerland) · 2023Review
- Environmental exposure of the general population to cadmium as a risk factor of the damage to the nervous system: A critical review of current data.Journal of applied toxicology : JAT · 2023Review
- Mercury Toxicity and Neurogenesis in the Mammalian Brain.International journal of molecular sciences · 2021Review
- Epigenetic influence of environmentally neurotoxic metals.Neurotoxicology · 2020Review
- Nuclear factor erythroid 2 - related factor 2 and its relationship with cellular response in nickel exposure: a systems biology analysis.BMC pharmacology & toxicology · 2019Article
- Comparative analysis of in vitro neurotoxicity of methylmercury, mercury, cadmium, and hydrogen peroxide on SH-SY5Y cells.The Journal of veterinary medical science · 2019Article
- An Eimeria acervulina OTU protease exhibits linkage-specific deubiquitinase activity.Parasitology research · 2019Article
- Arsenic-induced apoptosis in the p53-proficient and p53-deficient cells through differential modulation of NFkB pathway.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2018Article
- Article
- Coherent and Contradictory Facts, Feats and Fictions Associated with Metal Accumulation in Parkinson's Disease: Epicenter or Outcome, Yet a Demigod Question.Molecular neurobiology · 2017Review
- E3 Ubiquitin Ligases Neurobiological Mechanisms: Development to Degeneration.Frontiers in molecular neuroscience · 2017Review
- Genomic analysis of Ugandan and Rwandan chicken ecotypes using a 600 k genotyping array.BMC genomics · 2016Article
- The putative multidrug resistance protein MRP-7 inhibits methylmercury-associated animal toxicity and dopaminergic neurodegeneration in Caenorhabditis elegans.Journal of neurochemistry · 2014Article
- Comparative toxicogenomic responses of mercuric and methyl-mercury.BMC genomics · 2013Article
- Transcriptome sequencing (RNA-seq) analysis of the effects of metal nanoparticle exposure on the transcriptome of Chlamydomonas reinhardtii.Applied and environmental microbiology · 2013Article
- Low-level environmental cadmium exposure is associated with DNA hypomethylation in Argentinean women.Environmental health perspectives · 2012Article
- Oxidative stress in MeHg-induced neurotoxicity.Toxicology and applied pharmacology · 2011Review
- Cadmium induced p53-dependent activation of stress signaling, accumulation of ubiquitinated proteins, and apoptosis in mouse embryonic fibroblast cells.Toxicological sciences : an official journal of the Society of Toxicology · 2011Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Environmental and occupational exposures to heavy metals such as methylmercury (MeHg) and cadmium (Cd) pose significant health risks to humans, including neurotoxicity. The underlying mechanisms of their toxicity, however, remain to be fully characterized. Our previous studies with Cd and MeHg have demonstrated that the perturbation of the ubiquitin-proteasome system (UPS) was associated with metal-induced cytotoxicity and apoptosis. We conducted a microarray-based gene expression analysis to compare metal-altered gene expression patterns with a classical proteasome inhibitor, MG132 (0.5 microM), to determine whether the disruption of the UPS is a critical mechanism of metal-induced toxicity. We treated mouse embryonic fibroblast cells at doses of MeHg (2.5 microM) and Cd (5.0 microM) for 24 h. The doses selected were based on the neutral red-based cell viability assay where initial statistically significant decreases in variability were detected. Following normalization of the array data, we employed multilevel analysis tools to explore the data, including group comparisons, cluster analysis, gene annotations analysis (gene ontology analysis), and pathway analysis using GenMAPP and Ingenuity Pathway Analysis (IPA). Using these integrated approaches, we identified significant gene expression changes across treatments within the UPS (Uchl1 and Ube2c), antioxidant and phase II enzymes (Gsta2, Gsta4, and Noq1), and genes involved in cell cycle regulation pathways (ccnb1, cdc2a, and cdc25c). Furthermore, pathway analysis revealed significant alterations in genes implicated in Parkinson's disease pathogenesis following metal exposure. This study suggests that these pathways play a critical role in the development of adverse effects associated with metal exposures.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.