ArticleToxicology reports2014
Transcriptome-metabolome wide association study (TMWAS) of maneb and paraquat neurotoxicity reveals network level interactions in toxicologic mechanism.
Article in Toxicology reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.The Journal of clinical endocrinology and metabolism · 2016Trial
- Advancing translational exposomics: bridging genome, exposome and personalized medicine.Human genomics · 2025Review
- Redox organization of living systems.Free radical biology & medicine · 2024Review
- Systemic and Lung Inflammation and Oxidative Stress Associated With Behavioral Changes Induced by Inhaled Paraquat Are Ameliorated by Carvacrol.PPAR research · 2024Article
- Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese.Antioxidants (Basel, Switzerland) · 2023Article
- Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease.Acta pharmaceutica Sinica. B · 2022Review
- Multi-omic landscaping of human midbrains identifies disease-relevant molecular targets and pathways in advanced-stage Parkinson's disease.Clinical and translational medicine · 2022Article
- Lipid Remodeling Reveals the Adaptations of a Marine Diatom to Ocean Acidification.Frontiers in microbiology · 2021Article
- Maneb alters central carbon metabolism and thiol redox status in a toxicant model of Parkinson's disease.Free radical biology & medicine · 2021Article
- Metabolome Wide Association Study of serum DDT and DDE in Pregnancy and Early Postpartum.Reproductive toxicology (Elmsford, N.Y.) · 2020Article
- Benomyl, a benzimidazole fungicide, induces oxidative stress and apoptosis in neural cells.Toxicology reports · 2020Article
- Metabolome-Wide Association Study of Deployment to Balad, Iraq or Bagram, Afghanistan.Journal of occupational and environmental medicine · 2019Article
- Metabolomic Responses to Manganese Dose in SH-SY5Y Human Neuroblastoma Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2019Article
- Toxicant-mediated redox control of proteostasis in neurodegeneration.Current opinion in toxicology · 2019Article
- Genetic polymorphisms as determinants of pesticide toxicity: Recent advances.Toxicology reports · 2019Review
- Reducing oxidative toxicity of L-dopa in combination with two different antioxidants: an essential oil isolated from Rosa Damascena Mill., and vitamin C.Toxicology reports · 2019Article
- Protective mechanism of 1-methylhydantoin against lung injury induced by paraquat poisoning.PloS one · 2019Article
- Selenium at the redox interface of the genome, metabolome and exposome.Free radical biology & medicine · 2018Review
- Selenium supplementation prevents metabolic and transcriptomic responses to cadmium in mouse lung.Biochimica et biophysica acta. General subjects · 2018Article
- Acute Maneb Exposure Significantly Alters Both Glycolysis and Mitochondrial Function in Neuroblastoma Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
A combination of the herbicide paraquat (PQ) and fungicide maneb (MB) has been linked to Parkinson's disease. Previous studies show that this involves an additive toxicity with at least two different mechanisms. However, detailed understanding of mixtures is often difficult to elucidate because of the multiple ways by which toxic agents can interact. In the present study, we used a combination of transcriptomics and metabolomics to investigate mechanisms of toxicity of PQ and MB in a neuroblastoma cell line. Conditions were studied with concentrations of PQ and MB that each individually caused 20% cell death and together caused 50% cell death. Transcriptomic and metabolomic samples were collected at time points prior to significant cell death. Statistical and bioinformatic methods were applied to the resulting 30,869 transcripts and 1358 metabolites. Results showed that MB significantly changed more transcripts and metabolites than PQ, and combined PQ + MB impacted more than MB alone. Transcriptome-metabolome-wide association study (TMWAS) showed that significantly changed transcripts and metabolites mapped to two network substructures, one associating with significant effects of MB and the other included features significantly associated with PQ + MB. The latter contained 4 clusters of genes and associated metabolites, with one containing genes for two cation transporters and a cation transporter regulatory protein also recognized as a pro-apoptotic protein. Other clusters included stress response genes and transporters linked to cytoprotective mechanisms. MB also had a significant network structure linked to cell proliferation. Together, the results show that the toxicologic mechanism of the combined neurotoxicity of PQ and MB involves network level interactions and that TMWAS provides an effective approach to investigate such complex mechanisms.
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