ArticleToxicological sciences : an official journal of the Society of Toxicology2017
From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 61 citations in OpenAlex.
- Early-Life Rotenone Exposure Enhances Nigrostriatal Vulnerability and Parkinsonian Neurodegeneration in Aging Rats.Toxics · 2026Article
- Role of manganese in brain health and disease: Focus on oxidative stress.Free radical biology & medicine · 2025Review
- Rotenone Exposure During Development Conditions Parkinsonian Phenotype in Young Adult Rats.Toxics · 2025Article
- Gut to brain: essential micronutrient and trace element manganese transport, function and toxicity.Frontiers in physiology · 2025Review
- The Neuroanatomy of Induced Pluripotent Stem Cells: In Vitro Models of Subcortical Nuclei in Neurodegenerative Disorders.Current issues in molecular biology · 2024Review
- Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies.International journal of molecular sciences · 2024Review
- Effects of Chronic Exposure to Low Doses of Rotenone on Dopaminergic and Cholinergic Neurons in the CNS ofInternational journal of molecular sciences · 2024Article
- Rescue of impaired blood-brain barrier in tuberous sclerosis complex patient derived neurovascular unit.Journal of neurodevelopmental disorders · 2024Article
- Contractile and Genetic Characterization of Cardiac Constructs Engineered from Human Induced Pluripotent Stem Cells: Modeling of Tuberous Sclerosis Complex and the Effects of Rapamycin.Bioengineering (Basel, Switzerland) · 2024Article
- Rescue of Impaired Blood-Brain Barrier in Tuberous Sclerosis Complex Patient Derived Neurovascular Unit.bioRxiv : the preprint server for biology · 2023Article
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- LRRK2 Knockout Confers Resistance in HEK-293 Cells to Rotenone-Induced Oxidative Stress, Mitochondrial Damage, and Apoptosis.International journal of molecular sciences · 2023Article
- Fluorescence microscopy imaging of mitochondrial metabolism in cancer cells.Frontiers in oncology · 2023Review
- Reprogramming of adult human dermal fibroblasts to induced dorsal forebrain precursor cells maintains aging signatures.Frontiers in cellular neuroscience · 2023Article
- Systemic Rotenone Administration Causes Extra-Nigral Alterations in C57BL/6 Mice.Biomedicines · 2022Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Genomic, transcriptomic, and metabolomic profiles of hiPSC-derived dopamine neurons from clinically discordant brothers with identical PRKN deletions.NPJ Parkinson's disease · 2022Article
- Manganese-induced hyperactivity and dopaminergic dysfunction depend on age, sex and YAC128 genotype.Pharmacology, biochemistry, and behavior · 2022Article
- Patient-Specific iPSCs-Based Models of Neurodegenerative Diseases: Focus on Aberrant Calcium Signaling.International journal of molecular sciences · 2022Review
- A bistable, multiport valve enables microformulators creating microclinical analyzers that reveal aberrant glutamate metabolism in astrocytes derived from a tuberous sclerosis patient.Sensors and actuators. B, Chemical · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Parkinson's disease (PD) is the result of complex interactions between genetic and environmental factors. Two chemically distinct environmental stressors relevant to PD are the metal manganese and the pesticide rotenone. Both are thought to exert neurotoxicity at least in part via oxidative stress resulting from impaired mitochondrial activity. Identifying shared mechanism of action may reveal clues towards an understanding of the mechanisms underlying PD pathogenesis. Here we compare the effects of manganese and rotenone in human-induced pluripotent stem cells-derived postmitotic mesencephalic dopamine neurons by assessing several different oxidative stress endpoints. Manganese, but not rotenone caused a concentration and time-dependent increase in intracellular reactive oxygen/nitrogen species measured by quantifying the fluorescence of oxidized chloromethyl 2',7'-dichlorodihydrofluorescein diacetate (DCF) assay. In contrast, rotenone but not manganese caused an increase in cellular isoprostane levels, an indicator of lipid peroxidation. Manganese and rotenone both caused an initial decrease in cellular reduced glutathione; however, glutathione levels remained low in neurons treated with rotenone for 24 h but recovered in manganese-exposed cells. Neurite length, a sensitive indicator of overall neuronal health was adversely affected by rotenone, but not manganese. Thus, our observations suggest that the cellular oxidative stress evoked by these 2 agents is distinct yielding unique oxidative stress signatures across outcome measures. The protective effect of rasagiline, a compound used in the clinic for PD, had negligible impact on any of oxidative stress outcome measures except a subtle significant decrease in manganese-dependent production of reactive oxygen/nitrogen species detected by the DCF assay.
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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.