Effects of Organochlorine Insecticides on MAP Kinase Pathways in Human HaCaT Keratinocytes: Key Role of Reactive Oxygen Species

Ledirac, Nathalie; Anthérieu, Sébastien; d'Uby, Anne Dupuy; Caron, Jean-Claude; Rahmani, Roger

doi:10.1093/toxsci/kfi192

Cited by 56 publications

(43 citation statements)

References 37 publications

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“…The complexities of the physiological roles of MAPK may be due partially to the duration of MAPK activities differentially regulating genes in various cell types. Activation of ERK1/2 by organochlorine pesticides has been reported in human keratinocytes (Ledirac et al, 2005). It has been suggested that in situations where ERK1/2 induces cell death, the activation tends to be sustained (Wang et al, 2000), which is the case under our experimental conditions.…”

Section: )supporting

confidence: 62%

“…A critical role of ROS in organochlorine pesticidesinduced ERK1/2 activation, probably by stabilizing its phosphorylation, has been reported (Ledirac et al, 2005). It has been proposed that transient activation of ROS inactivates MAPK regulatory phosphatases, contributing to their activation, (Lee and Esselman, 2002).…”

Section: Page 22 Of 44 Toxicological Sciencesmentioning

confidence: 99%

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Reactive Oxygen Species and Extracellular Signal-Regulated Kinase 1/2 Mediate Hexachlorobenzene-Induced Cell Death in FRTL-5 Rat Thyroid Cells

Chiappini

Pontillo

Randi

et al. 2013

Toxicological Sciences

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Section: )supporting

confidence: 62%

Section: Page 22 Of 44 Toxicological Sciencesmentioning

confidence: 99%

Reactive Oxygen Species and Extracellular Signal-Regulated Kinase 1/2 Mediate Hexachlorobenzene-Induced Cell Death in FRTL-5 Rat Thyroid Cells

Chiappini

Pontillo

Randi

et al. 2013

Toxicological Sciences

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“…PKC-mediated internalization also appears to reduce recycling of DAT pools and increase degradation via the lysosomal pathway (Daniels & Amara, 1999;Loder & Melikian, 2003), thereby decreasing the total DAT levels in the cell. Interestingly, dieldrin exposure in cells can lead to the activation of a specific PKC isoform Ledirac et al, 2005) which could explain the decreased DAT expression seen in the striatum.…”

Section: Discussionmentioning

confidence: 99%

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Hatcher

Richardson

Guillot

et al. 2007

Experimental Neurology

135

107

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Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3 H-WIN 35,428 binding and 3 H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. *Corresponding Author: Gary W. Miller, Ph.D., Emory University -Center for Neurodegenerative Disease, Whitehead Biomedical Research Building 505K, 615 Michael Street Atlanta, GA 30322, Phone: 404.712.8582, Fax: 404.727.3728, Email: gary.miller@emory.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Parkinson's disease (PD) is a chronic, progressive neurological disorder clinically characterized by resting tremor, bradykinesia, postural instability and rigidity (Marsden, 1984). Pathologically, PD presents as dopaminergic neuronal loss in the substantia nigra pars compacta (SNc), striatal depletion of the neurotransmitter dopamine (DA), the loss of neurochemical markers, such as the dopamine transporter (DAT), and the presence of Lewy bodies containing α-synuclein (Spillantini et al., 1997). Because only 5-10% of PD cases are thought to be primarily genetic in origin, investigation of the role of environmental factors in the pathogenesis of the disease is warranted (Dauer & Przedborski, 2003). NIH Public AccessNumerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing PD Le Couteur et al., 1999;Priyadarshi et al., 2000;Semchuk et al., 1991Semchuk et al., ,1992. In addition, a correlation between the presence of th...

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“…The carcinogenic potential of pyrethroids was also reported on the murine model (9). A few recent studies revealed that besides blocking neurotransmission, both pyrethroids and organophosphate pesticides can cause immunosuppression and deregulation of many signalling molecules (10)(11)(12)(13)(14)(15). Organophosphates (derivatives of phosphonic acid) and systemic azole fungicides have profound cytotoxic activities, too (16,17).…”

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confidence: 99%

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model

Chaklader¹,

Das²,

Pereira³

et al. 2012

Archives of Industrial Hygiene and Toxicology

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The mechanistic interplay between pesticide exposure and development of marrow aplasia is not yet well established but there are indices that chronic pesticide exposure in some instances causes marrow aplasia like haematopoietic degenerative condition in human beings. Canonical Hedgehog (Hh) signalling has multiple roles in a wide range of developmental processes, including haematopoiesis. The present study was designed to explore the status of four important components of the canonical Hedgehog signalling cascade, the Sonic Hedgehog (Shh), Ptch1, Smo, and Gli1, in a mouse model of chronic pesticide-induced bone marrow aplasia. We used 5 % aqueous mixture of pesticides (chlorpyriphos, prophenophos, cypermethrin, alpha-methrin, and hexaconazole) for inhalation and dermal exposure of 6 hours per day and 5 days a week up to 90 days. Murine bone marrow aplasia related to chronic pesticide treatment was confi rmed primarily by haemogram, bone marrow cellularity, short term bone marrow explant culture for cellular kinetics, bone marrow smear, and fl ow cytometric Lin -Sca-1 + C-kit + extracellular receptor expression pattern. Later, components of hedgehog signalling were analysed in the bone marrow of both control and pesticide-treated aplastic groups of animals. The results depicted pancytopenic feature of peripheral blood, developmental anomaly of neutrophils, depression of primitive stem and progenitor population along with Shh, Ptch1, Smo and Gli1 expression in aplasia group. This investigation suggests that pesticide-induced downregulation of two critically important proteins -Ptch1 and Gli1 -inside the haematopoietic stem and progenitor cell population impairs haematopoietic homeostasis and regeneration mechanism in vivo concurrent with bone marrow aplasia. Arh Hig Rada Toksikol 2012;63:271-282 A surge of numerous organophosphates, pyrethroids (analogs of naturally occurring phytopyrethrins), and thiazole fungicides replaced DDT after the ban in 1993. Depending on the physiological activity, synthetic pyrethroids are of two distinct types: Type I pyrethroids, which do not contain the α-cyano group, and Type II pyrethroids, which have the α-cyano group (1-3). Previous studies have affi rmed the genotoxic and/or cytotoxic effects of Type II pyrethroids such as cyfl uthrin, cypermethrin etc. (4-9). The carcinogenic potential of pyrethroids was also reported on the murine model (9). A few recent studies revealed that besides blocking neurotransmission, both pyrethroids and organophosphate pesticides can cause Unauthenticated Download Date | 5/12/18 12:23 AM KEY WORDS: bone marrow suppression, haematopoietic stem cell, patched, smoothened, sonic hedgehog Chaklader M, et al. ALTERED HH-GLI SIGNALLING IN PESTICIDE-INDUCED BONE MARROW APLASIA

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Effects of Organochlorine Insecticides on MAP Kinase Pathways in Human HaCaT Keratinocytes: Key Role of Reactive Oxygen Species

Cited by 56 publications

References 37 publications

Reactive Oxygen Species and Extracellular Signal-Regulated Kinase 1/2 Mediate Hexachlorobenzene-Induced Cell Death in FRTL-5 Rat Thyroid Cells

Reactive Oxygen Species and Extracellular Signal-Regulated Kinase 1/2 Mediate Hexachlorobenzene-Induced Cell Death in FRTL-5 Rat Thyroid Cells

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model

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