ArticleToxicological sciences : an official journal of the Society of Toxicology2011
Mechanism of pyrethroid pesticide-induced apoptosis: role of calpain and the ER stress pathway.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 140 citations in OpenAlex.
- Gestational deltamethrin exposure exacerbates post-traumatic epileptiform activity and social deficits, diminishing the therapeutic efficacy of curcumin in rats.Metabolic brain disease · 2026Article
- Pollutant-regulated mitophagy: new perspectives in environmental toxicology.Apoptosis : an international journal on programmed cell death · 2026Review
- Combined Neurotoxic Effects of Commercial Formulations of Pyrethroid (Deltamethrin) and Neonicotinoid (Imidacloprid) Pesticides on Adult Zebrafish (Life (Basel, Switzerland) · 2025Article
- Implication of Pyrethroid Neurotoxicity for Human Health: A Lesson from Animal Models.Neurotoxicity research · 2024Review
- Key role of mitochondrial mutation Leu107Ser (COX1) in deltamethrin resistance in salmon lice (Lepeophtheirus salmonis).Scientific reports · 2022Article
- Deltamethrin-Evoked ER Stress Promotes Neuroinflammation in the Adult Mouse Hippocampus.Cells · 2022Article
- Current understandings and perspectives of petroleum hydrocarbons in Alzheimer's disease and Parkinson's disease: a global concern.Environmental science and pollution research international · 2022Review
- Developmental deltamethrin: Sex-specific hippocampal effects in Sprague Dawley rats.Current research in toxicology · 2022Article
- Genome-Wide Selective Signature Analysis Revealed Insecticide Resistance Mechanisms inInsects · 2021Article
- Protective effects of rutin against deltamethrin-induced hepatotoxicity and nephrotoxicity in rats via regulation of oxidative stress, inflammation, and apoptosis.Environmental science and pollution research international · 2021Article
- Modulation of the Nitric Oxide/BH4 Pathway Protects Against Irradiation-Induced Neuronal Damage.Neurochemical research · 2021Article
- High-Resolution Metabolomic Assessment of Pesticide Exposure in Central Valley, California.Chemical research in toxicology · 2021Article
- Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery.Journal of personalized medicine · 2021Review
- Role of environmental pollutants in Alzheimer's disease: a review.Environmental science and pollution research international · 2020Review
- An epigenome-wide association study of ambient pyrethroid pesticide exposures in California's central valley.International journal of hygiene and environmental health · 2020Article
- Protective Role ofBiomolecules · 2020Article
- Single or combined exposure to chlorpyrifos and cypermethrin provoke oxidative stress and downregulation in monoamine oxidase and acetylcholinesterase gene expression of the rat's brain.Environmental science and pollution research international · 2020Article
- Nerve Growth Factor Protects Against Pyrethroid-Induced Endoplasmic Reticulum (ER) Stress in Primary Hippocampal Neurons.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- Neurotoxicity of pesticides.Acta neuropathologica · 2019Review
- Permethrin and ivermectin modulate lipid metabolism in steatosis-induced HepG2 hepatocyte.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2019Article
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2 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to the pyrethroid pesticide deltamethrin has been demonstrated to cause apoptosis both in vitro and in vivo. However, the molecular pathways leading to deltamethrin-induced apoptosis have not been established. To identify these pathways, SK-N-AS neuroblastoma cells were exposed to deltamethrin (100 nM-5 μM) for 24-48 h. Deltamethrin produced a time- and dose-dependent increase (21-300%) in DNA fragmentation, an indicator of apoptosis. Data demonstrate that the initiation of DNA fragmentation resulted from interaction of deltamethrin with Na⁺ channels and consequent calcium influx, as tetrodotoxin and the intracellular Ca²⁺ chelator BAPTA-AM completely prevented apoptosis. DNA fragmentation was accompanied by increased caspase-9 and -3 activities and was abolished by specific caspase-9 and -3 inhibitors. However, deltamethrin did not increase cytosolic cytochrome c levels, indicating that the mitochondrial pathway was likely not involved. Additional studies demonstrated that deltamethrin exposure activated caspase-12 activity and that pharmacological inhibition and siRNA knockdown of calpain prevented deltamethrin-induced DNA fragmentation, thus indicating a role for the endoplasmic reticulum (ER) stress pathway. This was confirmed by the observation that inhibition of eIF2α abolished deltamethrin-induced DNA fragmentation. Together, these data demonstrate that deltamethrin causes apoptosis through its interaction with Na⁺ channels, leading to calcium overload and activation of the ER stress pathway. Because ER stress and the subsequent unfolded protein response have been observed in a number of neurodegenerative diseases, these data provide mechanistic information by which high-level exposure to pyrethroids may contribute to neurodegeneration.
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