ArticleToxicological sciences : an official journal of the Society of Toxicology2013
Impairment of Atg5-dependent autophagic flux promotes paraquat- and MPP⁺-induced apoptosis but not rotenone or 6-hydroxydopamine toxicity.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 2 of them syntheses that pooled it.
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Who cites it
40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 64 citations in OpenAlex.
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- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
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- Parkinson's disease models and death signaling: what do we know until now?Frontiers in neuroanatomy · 2024Review
- Metformin and Trehalose-Modulated Autophagy Exerts a Neurotherapeutic Effect on Parkinson's Disease.Molecular neurobiology · 2023Article
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- Redox Regulation and Metabolic Dependency of Zika Virus Replication: Inhibition by Nrf2-Antioxidant Response and NAD(H) Antimetabolites.Journal of virology · 2023Article
- Dioscin-Mediated Autophagy Alleviates MPPMolecules (Basel, Switzerland) · 2022Article
- Calycosin Alleviates Paraquat-Induced Neurodegeneration by Improving Mitochondrial Functions and Regulating Autophagy in aAntioxidants (Basel, Switzerland) · 2022Article
- Idebenone improves motor dysfunction, learning and memory by regulating mitophagy in MPTP-treated mice.Cell death discovery · 2022Article
- Regulation of Heme Oxygenase and Its Cross-Talks with Apoptosis and Autophagy under Different Conditions inAntioxidants (Basel, Switzerland) · 2021Article
- Mitochondria-affecting small molecules ameliorate proteostasis defects associated with neurodegenerative diseases.Scientific reports · 2021Article
- Inhibition of Zika virus replication by G-quadruplex-binding ligands.Molecular therapy. Nucleic acids · 2021Article
- Mechanistic Target of Rapamycin Signaling Activation Antagonizes Autophagy To Facilitate Zika Virus Replication.Journal of virology · 2020Article
- Age-related Effects of Heroin on Gene Expression in the Hippocampus and Striatum of Cynomolgus Monkeys.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2020Article
- Autophagy Stimulation Decreases Dopaminergic Neuronal Death Mediated by Oxidative Stress.Molecular neurobiology · 2019Article
- Autophagy as a Homeostatic Mechanism in Response to Stress Conditions in the Central Nervous System.Molecular neurobiology · 2019Review
- Protective Effects of Kaempferol on D-Ribose-Induced Mesangial Cell Injury.Oxidative medicine and cellular longevity · 2019Article
- A new hypothesis for Parkinson's disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics.Molecular neurodegeneration · 2018Review
- mTOR/AMPK signaling in the brain: Cell metabolism, proteostasis and survival.Current opinion in toxicology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Controversial reports on the role of autophagy as a survival or cell death mechanism in dopaminergic cell death induced by parkinsonian toxins exist. We investigated the alterations in autophagic flux and the role of autophagy protein 5 (Atg5)-dependent autophagy in dopaminergic cell death induced by parkinsonian toxins. Dopaminergic cell death induced by the mitochondrial complex I inhibitors 1-methyl-4-phenylpyridinium (MPP⁺) and rotenone, the pesticide paraquat, and the dopamine analog 6-hydroxydopamine (6-OHDA) was paralleled by increased autophagosome accumulation. However, when compared with basal autophagy levels using chloroquine, autophagosome accumulation was a result of impaired autophagic flux. Only 6-OHDA induced an increase in autophagosome formation. Overexpression of a dominant negative form of Atg5 increased paraquat- and MPP⁺-induced cell death. Stimulation of mammalian target of rapamycin (mTOR)-dependent signaling protected against cell death induced by paraquat, whereas MPP⁺-induced toxicity was enhanced by wortmannin, a phosphoinositide 3-kinase class III inhibitor, rapamycin, and trehalose, an mTOR-independent autophagy activator. Modulation of autophagy by either pharmacological or genetic approaches had no effect on rotenone or 6-OHDA toxicity. Cell death induced by parkinsonian neurotoxins was inhibited by the pan caspase inhibitor (Z-VAD), but only caspase-3 inhibition was able to decrease MPP⁺-induced cell death. Finally, inhibition of the lysosomal hydrolases, cathepsins, increased the toxicity by paraquat and MPP⁺, supporting a protective role of Atg5-dependent autophagy and lysosomes degradation pathways on dopaminegic cell death. These results demonstrate that in dopaminergic cells, Atg5-dependent autophagy acts as a protective mechanism during apoptotic cell death induced by paraquat and MPP⁺ but not during rotenone or 6-OHDA toxicity.
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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.