ArticleToxicological sciences : an official journal of the Society of Toxicology2019
Metabolomic Responses to Manganese Dose in SH-SY5Y Human Neuroblastoma Cells.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Macronutrient, Energy, and Bile Acid Metabolism Pathways Altered Following a Physiological Meal Challenge, Relative to Fasting, among Guatemalan Adults.The Journal of nutrition · 2020Trial
- Cannabidiol Protects Against 1-Methyl-4-Phenylpyridinium and Manganese-Induced Neurotoxicity via Nod-Like Receptor Protein 3 Inflammasome Suppression.Journal of biochemical and molecular toxicology · 2026Article
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Manganese-based nanomaterials in diagnostics and chemodynamic therapy of cancers: new development.RSC advances · 2024Review
- Redox organization of living systems.Free radical biology & medicine · 2024Review
- The role of TFEB-mediated autophagy-lysosome dysfunction in manganese neurotoxicity.Current research in toxicology · 2024Article
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- Glutamine supplementation reverses manganese neurotoxicity by eliciting the mitochondrial unfolded protein response.iScience · 2023Article
- Antagonistic Interactions in Mitochondria ROS Signaling Responses to Manganese.Antioxidants (Basel, Switzerland) · 2023Article
- Advances in Ultra-High-Resolution Mass Spectrometry for Pharmaceutical Analysis.Molecules (Basel, Switzerland) · 2023Review
- The interaction of ammonia and manganese in abnormal metabolism of minimal hepatic encephalopathy: A comparison metabolomics study.PloS one · 2023Article
- The mitochondrial RNA granule modulates manganese-dependent cell toxicity.Molecular biology of the cell · 2022Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Manganese-Induced Neurotoxicity through Impairment of Cross-Talk Pathways in Human Neuroblastoma Cell LineToxics · 2021Article
- Metabolomics reveal alterations in arachidonic acid metabolism in Schistosoma mekongi after exposure to praziquantel.PLoS neglected tropical diseases · 2021Article
- Molecular Targets of Manganese-Induced Neurotoxicity: A Five-Year Update.International journal of molecular sciences · 2021Review
- Manganese-induced neurodegenerative diseases and possible therapeutic approaches.Expert review of neurotherapeutics · 2020Review
- ZIP14 is degraded in response to manganese exposure.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2019Article
- Transcriptome Analysis Reveals Distinct Responses to PhysiologicFrontiers in genetics · 2019Article
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8 authors at 1 institution in 1 country.
Funding
Abstract
Manganese (Mn)-associated neurotoxicity has been well recognized. However, Mn is also an essential nutrient to maintain physiological function. Our previous study of human neuroblastoma SH-SY5Y cells showed that Mn treatment comparable to physiological and toxicological concentrations in human brain resulted in different mitochondrial responses, yet cellular metabolic responses associated with such different outcomes remain uncharacterized. Herein, SH-SY5Y cells were examined for metabolic responses discriminated by physiological and toxicological levels of Mn using high-resolution metabolomics (HRM). Before performing HRM, we examined Mn dose (from 0 to100 μM) and time effects on cell death. Although we did not observe any immediate cell death after 5 h exposure to any of the Mn concentrations assessed (0-100 μM), cell loss was present after a 24-h recovery period in cultures treated with Mn ≥ 50 μM. Exposure to Mn for 5 h resulted in a wide range of changes in cellular metabolism including amino acids (AA), neurotransmitters, energy, and fatty acids metabolism. Adaptive responses at 10 μM showed increases in neuroprotective AA metabolites (creatine, phosphocreatine, phosphoserine). A 5-h exposure to 100 µM Mn, a time before any cell death occurred, resulted in decreases in energy and fatty acid metabolites (hexose-1,6 bisphosphate, acyl carnitines). The results show that adjustments in AA metabolism occur in response to Mn that does not cause cell death while disruption in energy and fatty acid metabolism occur in response to Mn that results in subsequent cell death. The present study establishes utility for metabolomics analyses to discriminate adaptive and toxic molecular responses in a human in vitro cellular model that could be exploited in evaluation of Mn toxicity.
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