Dieldrin-induced neurotoxicity involves impaired mitochondrial bioenergetics and an endoplasmic reticulum stress response in rat dopaminergic cells

Schmidt, J; Rushin, Anna; Boyda, Jonna; Souders, Christopher L.; Martyniuk, Christopher J.

doi:10.1016/j.neuro.2017.08.007

Cited by 27 publications

(14 citation statements)

References 45 publications

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“…In another study, dieldrin between 5 and 25 μM has been shown to affect endpoints related to mitochondrial dysfunction and apoptosis in rat dopaminergic cell lines in combination with other organochlorines (Sharma et al, 2009). More recently, a study exposing dopaminergic rat cells (N27) to 25 μM dieldrin for 24 h revealed a 40–50% reduction in oxygen consumption rates of cells following the addition of mitochondrial toxicants into the culture, further evidence that dieldrin impairs mitochondrial bioenergetics in dopamine cells (Schmidt et al, 2017). Noteworthy was that this response was also associated with a 3-fold induction of transcript levels for Chop/Gadd153 (DNA Damage Inducible Transcript 3), an apoptotic gene activated under endoplasmic reticulum (ER) stress.…”

Section: Pesticidesmentioning

confidence: 95%

“…Dysfunction in these receptors result in over-excitation, seizures, and death. Studies have shown some activity as a mitochondrial toxicant (Schmidt et al, 2017) and endocrine disruptor, and dieldrin has been reported to disrupt the mitochondrial electron transport chain (Pardini et al, 1971) and to act as weak estrogen receptor agonists and antagonists (Andersen et al, 2002) in estrogen and androgen transactivation assays. Detailed structure-activity relationships have also been investigated for dieldrin in terms of cellular interactions and dieldrin was found to disrupt a wide number of cellular processes including the dopamine synthesis pathway that were dependent upon both its stereochemistry and structure (Allen et al, 2013).…”

Section: Pesticidesmentioning

confidence: 99%

“…The precise mechanisms underlying the relationship between neuroactive pesticides and pathological conditions associated with neurodegenerative disease are many and include aberrant redox cycling and oxidative damage, mitochondrial dysfunction, ATP deficits, impaired unfolded protein response, neuroinflammation, and metabolic disruption among others (Sun et al, 2005; Castello et al, 2007; Hatcher et al, 2007; Cristóvão et al, 2009; Franco et al, 2010; Roede et al, 2011; Lei et al, 2014; Caito and Aschner, 2015; Cowie et al, 2017a,b). Mitochondrial dysfunction is well documented to contribute to dopaminergic cell death and PD pathology (Camilleri and Vassallo, 2014; Huang et al, 2016; Helley et al, 2017; Schmidt et al, 2017) and studies have identified specific genetic correlates (i.e., PARK genes) associated with the etiopathogenetic nature of the disease (reviewed in Helley et al, 2017). Understanding the role of specific signaling pathways under low, chronic pesticide exposures (i.e., exposome) is an important facet for understanding how our environment contributes to PD and other neurodegenerative diseases.…”

Section: Introductionmentioning

confidence: 99%

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Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance

et al. 2019

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While a number of genetic mutations are associated with Parkinson's disease (PD), it is also widely acknowledged that the environment plays a significant role in the etiology of neurodegenerative diseases. Epidemiological evidence suggests that occupational exposure to pesticides (e.g., dieldrin, paraquat, rotenone, maneb, and ziram) is associated with a higher risk of developing PD in susceptible populations. Within dopaminergic neurons, environmental chemicals can have an array of adverse effects resulting in cell death, such as aberrant redox cycling and oxidative damage, mitochondrial dysfunction, unfolded protein response, ubiquitin-proteome system dysfunction, neuroinflammation, and metabolic disruption. More recently, our understanding of how pesticides affect cells of the central nervous system has been strengthened by computational biology. New insight has been gained about transcriptional and proteomic networks, and the metabolic pathways perturbed by pesticides. These networks and cell signaling pathways constitute potential therapeutic targets for intervention to slow or mitigate neurodegenerative diseases. Here we review the epidemiological evidence that supports a role for specific pesticides in the etiology of PD and identify molecular profiles amongst these pesticides that may contribute to the disease. Using the Comparative Toxicogenomics Database, these transcripts were compared to those regulated by the PD-associated neurotoxicant MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). While many transcripts are already established as those related to PD (alpha-synuclein, caspases, leucine rich repeat kinase 2, and parkin2), lesser studied targets have emerged as “pesticide/PD-associated transcripts” [e.g., phosphatidylinositol glycan anchor biosynthesis class C (Pigc), allograft inflammatory factor 1 (Aif1), TIMP metallopeptidase inhibitor 3, and DNA damage inducible transcript 4]. We also compared pesticide-regulated genes to a recent meta-analysis of genome-wide association studies in PD which revealed new genetic mutant alleles; the pesticides under review regulated the expression of many of these genes (e.g., ELOVL fatty acid elongase 7, ATPase H+ transporting V0 subunit a1, and bridging integrator 3). The significance is that these proteins may contribute to pesticide-related increases in PD risk. This review collates information on transcriptome responses to PD-associated pesticides to develop a mechanistic framework for quantifying PD risk with exposures.

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Section: Pesticidesmentioning

confidence: 95%

Section: Pesticidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance

et al. 2019

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“…Organochlorine pesticides are highly carcinogenic and generate oxidative stress and mitochondrial cell malfunction (SCHMIDT et al, 2017), while carbamates lead to apoptosis (cell self-destruction) and the development of tumor cells in the central nervous system (PIEL et al, 2019). The widespread and poorly administered use of pesticides has increased the resistance of certain plant species to herbicides.…”

Section: Introductionmentioning

confidence: 99%

Nano-Delivery Systems of Pesticides Active Agents for Agriculture Applications - An Overview

Oliveira¹,

Mulinari²,

Reichert³

et al. 2020

Ciência, Tecnologia E Inovação: Do Campo À Mesa

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Agricultural protection agents used in soil and crops, when applied conventionally, may have their activity impaired against pests and vectors due to their volatilization, photodegradation, leaching, and other unwanted occurrences caused by weather conditions. These problems cause economic and environmental damage due to the high volume of applications necessary for the farmer to achieve the desired results. The indiscriminate use of free pesticides causes high environmental pollution because these compounds are cumulative in soil, water and vegetation, sometimes causing air contamination, which can cause health issues in local workers and the death of animals. In contrast, nanopesticides are an alternative emerging technology that allows the controlled release of active compounds, improving pest control performance and turning it more sustainable and in line with the concept of precision agriculture. The use of nano-delivery systems for pesticide agents uses nanostructures capable of altering the release kinetics of these compounds, providing the plantation with an adequate amount for pest elimination. This paper presents an overview of nanopesticides, addresses some current concepts of sustainability, reviews and analyzes the latest developments regarding these nanomaterials, and provides an update on their advantages and disadvantages.

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“…In humans, direct exposure to organophosphate pesticides can lead to the appearance of lymphomas (KOUTROS et al, 2019). Organochlorine pesticides are highly carcinogenic and generate oxidative stress and mitochondrial cell malfunction (SCHMIDT et al, 2017), while carbamates lead to apoptosis (cell selfdestruction) and the development of tumor cells in the central nervous system (PIEL et al, 2019). The widespread and poorly administered use of pesticides has increased the resistance of certain plant species to herbicides.…”

Section: Introductionmentioning

confidence: 99%

Nano-Delivery Systems of Pesticides Active Agents for Agriculture Applications - An Overview

de¹,

Mulinari²,

Wilson³

et al. 2020

Ciência, Tecnologia E Inovação: Do Campo À Mesa

View full text Add to dashboard Cite

Agricultural protection agents used in soil and crops, when applied conventionally, may have their activity impaired against pests and vectors due to their volatilization, photodegradation, leaching, and other unwanted occurrences caused by weather conditions. These problems cause economic and environmental damage due to the high volume of applications necessary for the farmer to achieve the desired results. The indiscriminate use of free pesticides causes high environmental pollution because these compounds are cumulative in soil, water and vegetation, sometimes causing air contamination, which can cause health issues in local workers and the death of animals. In contrast, nanopesticides are an alternative emerging technology that allows the controlled release of active compounds, improving pest control performance and turning it more sustainable and in line with the concept of precision agriculture. The use of nanodelivery systems for pesticide agents uses nanostructures capable of altering the release kinetics of these compounds, providing the plantation with an adequate amount for pest elimination. This paper presents an overview of nanopesticides, addresses some current concepts of sustainability, reviews and analyzes the latest developments regarding these nanomaterials, and provides an update on their advantages and disadvantages.

show abstract

Dieldrin-induced neurotoxicity involves impaired mitochondrial bioenergetics and an endoplasmic reticulum stress response in rat dopaminergic cells

Cited by 27 publications

References 45 publications

Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance

Elucidating Conserved Transcriptional Networks Underlying Pesticide Exposure and Parkinson's Disease: A Focus on Chemicals of Epidemiological Relevance

Nano-Delivery Systems of Pesticides Active Agents for Agriculture Applications - An Overview

Nano-Delivery Systems of Pesticides Active Agents for Agriculture Applications - An Overview

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