ArticleToxicology2015
JNK inhibition of VMAT2 contributes to rotenone-induced oxidative stress and dopamine neuron death.
Article in Toxicology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pre-clinical Studies Identifying Molecular Pathways of Neuroinflammation in Parkinson's Disease: A Systematic Review.Frontiers in aging neuroscience · 2022Pooled it
- Inhibition of pro-apoptotic UPR pathways PERK/CHOP and IRE1/JNK protects differentiated SH-SY5Y cells against rotenone-induced toxicity.Frontiers in molecular neuroscience · 2025Article
- A systematic exploration of unexploited genes for oxidative stress in Parkinson's disease.NPJ Parkinson's disease · 2024Article
- Dimethyl itaconate ameliorates cognitive impairment induced by a high-fat diet via the gut-brain axis in mice.Microbiome · 2023Article
- Micro- and Nano-Systems Developed for Tolcapone in Parkinson's Disease.Pharmaceutics · 2022Article
- 1,5-Anhydro-D-fructose Protects against Rotenone-Induced Neuronal Damage In Vitro through Mitochondrial Biogenesis.International journal of molecular sciences · 2021Article
- Genetic or Toxicant-Induced Disruption of Vesicular Monoamine Storage and Global Metabolic Profiling in Caenorhabditis elegans.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Clinically Precedented Protein Kinases: Rationale for Their Use in Neurodegenerative Disease.Frontiers in aging neuroscience · 2020Review
- Neurotoxicity of the pesticide rotenone on neuronal polarization: a mechanistic approach.Neural regeneration research · 2019Review
- Icariin-mediated activation of autophagy confers protective effect on rotenone induced neurotoxicity in vivo and in vitro.Toxicology reports · 2019Article
- Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.Inflammopharmacology · 2018Article
- Sarm1 induction and accompanying inflammatory response mediates age-dependent susceptibility to rotenone-induced neurotoxicity.Cell death discovery · 2018Article
- Protective Effect of Curcumin by Modulating BDNF/DARPP32/CREB in Arsenic-Induced Alterations in Dopaminergic Signaling in Rat Corpus Striatum.Molecular neurobiology · 2018Article
- Dopaminergic Dysfunction in Mammalian Dopamine Neurons Induced by Simazine Neurotoxicity.International journal of molecular sciences · 2017Article
- Nanotechnology-based drug delivery of ropinirole for Parkinson's disease.Drug delivery · 2017Article
- Impact of Plant-Derived Flavonoids on Neurodegenerative Diseases.Neurotoxicity research · 2016Review
- Polymorphism in the Vesicular Monoamine Transporter 2 Gene Decreases the Risk of Parkinson's Disease in Han Chinese Men.Parkinson's disease · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Treatment with rotenone, both in vitro and in vivo, is widely used to model dopamine neuron death in Parkinson's disease upon exposure to environmental neurotoxicants and pesticides. Mechanisms underlying rotenone neurotoxicity are still being defined. Our recent studies suggest that rotenone-induced dopamine neuron death involves microtubule destabilization, which leads to accumulation of cytosolic dopamine and consequently reactive oxygen species (ROS). Furthermore, the c-Jun N-terminal protein kinase (JNK) is required for rotenone-induced dopamine neuron death. Here we report that the neural specific JNK3 isoform of the JNKs, but not JNK1 or JNK2, is responsible for this neuron death in primary cultured dopamine neurons. Treatment with taxol, a microtubule stabilizing agent, attenuates rotenone-induced phosphorylation and presumably activation of JNK. This suggests that JNK is activated by microtubule destabilization upon rotenone exposure. Moreover, rotenone inhibits VMAT2 activity but not VMAT2 protein levels. Significantly, treatment with SP600125, a pharmacological inhibitor of JNKs, attenuates rotenone inhibition of VMAT2. Furthermore, decreased VMAT2 activity following in vitro incubation of recombinant JNK3 protein with purified mesencephalic synaptic vesicles suggests that JNK3 can inhibit VMAT2 activity. Together with our previous findings, these results suggest that rotenone induces dopamine neuron death through a series of sequential events including microtubule destabilization, JNK3 activation, VMAT2 inhibition, accumulation of cytosolic dopamine, and generation of ROS. Our data identify JNK3 as a novel regulator of VMAT2 activity.
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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.