Decreased arginine methylation and myelin alterations in arsenic exposed rats

Zarazúa, Sergio; Ríos, Rosalva; Delgado, Juan Manuel; Santoyo, Martha; Ortiz-Pérez, Deogracias; Jiménez‐Capdeville, María E.

doi:10.1016/j.neuro.2009.10.014

Cited by 49 publications

(17 citation statements)

References 55 publications

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“…In an experimental study of myelin alteration in rats exposed to iAs via drinking water (36 µg/mL), plasma ADMA was significantly increased 4 months after treatment compared with the control group [9.7 ± 0.6 vs. 3.4 ± 0.6 nmol/mL (Zarazua et al 2010)].…”

Section: Discussionmentioning

confidence: 99%

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

Osorio-Yáñez

Ayllon-Vergara

Aguilar-Madrid

et al. 2013

Environ Health Perspect

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Background: Arsenic exposure is a risk factor for atherosclerosis in adults, but there is little information on arsenic and early risk biomarkers for atherosclerosis in children. Carotid intima-media thickness (cIMT) is an indicator of subclinical atherosclerotic burden that has been associated with plasma asymmetric dimethylarginine (ADMA), a predictor of cardiovascular disease risk.Objectives: The aim of this study was to investigate associations of arsenic exposure with cIMT, ADMA, and endothelial adhesion molecules [soluble intercellular cell adhesion molecule-1 (sICAM-1); soluble vascular cell adhesion molecule-1 (sVCAM-1)] in children who had been exposed to environmental inorganic arsenic (iAs).Methods: We conducted a cross-sectional study in 199 children 3–14 years of age who were residents of Zimapan, México. We evaluated cIMT using ultrasonography, and plasma lipid profiles by standard methods. We analyzed ADMA, sICAM-1, and sVCAM-1 by ELISA, and measured the concentrations of total speciated arsenic (tAs) in urine using hydride generation cryotrapping atomic absorption spectrometry.Results: In the multiple linear regression model for cIMT, tAs categories were positively associated with cIMT increase. The estimated cIMT diameter was greater in 35- to 70-ng/mL and > 70-ng/mL groups (0.035 mm and 0.058 mm per 1-ng/mL increase in urinary tAs, respectively), compared with the < 35-ng/mL group. In addition to tAs level, plasma ADMA was a significant predictor of cIMT. In the adjusted regression model, cIMT, percent iAs, and plasma sVCAM-1 were significant predictors of ADMA levels (e.g., 0.419-μmol/L increase in ADMA per 1-mm increase in cIMT).Conclusions: Arsenic exposure and plasma ADMA levels were positively associated with cIMT in a population of Mexican children with environmental arsenic exposure through drinking water.Citation: Osorio-Yáñez C, Ayllon-Vergara JC, Aguilar-Madrid G, Arreola-Mendoza L, Hernández-Castellanos E, Barrera-Hernández A, De Vizcaya-Ruíz A, Del Razo LM. 2013. Carotid intima-media thickness and plasma asymmetric dimethylarginine in Mexican children exposed to inorganic arsenic. Environ Health Perspect 121:1090–1096; http://dx.doi.org/10.1289/ehp.1205994

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Section: Discussionmentioning

confidence: 99%

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

Osorio-Yáñez

Ayllon-Vergara

Aguilar-Madrid

et al. 2013

Environ Health Perspect

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“…Rodent studies with prenatal exposure to 100 μg/L arsenic demonstrated reduced global acetylation on lysine 9 of histone 3 (H3K9ac) in the cortex and hippocampus of postnatal day (PND1) pups, which was correlated to altered learning in adulthood [63]. Exposure to 3 and 36 ppm arsenic throughout development up to four months reduced myelination (for which methylation is required) and dimethylation of arginine residues on histones [64]. This could result from the altered expression and function of epigenetic modifiers or transcription factors, as arsenic impacts zinc-finger protein expression and function [65].…”

Section: Mechanisms Of Actionmentioning

confidence: 99%

The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review

Tyler

Allan

2014

Curr Envir Health Rpt

431

233

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Arsenic toxicity is a worldwide health concern as several millions of people are exposed to this toxicant via drinking water, and exposure affects almost every organ system in the body including the brain. Recent studies have shown that even low concentrations of arsenic impair neurological function, particularly in children. This review will focus on the current epidemiological evidence of arsenic neurotoxicity in children and adults, with emphasis on cognitive dysfunction, including learning and memory deficits and mood disorders. We provide a cohesive synthesis of the animal studies that have focused on neural mechanisms of dysfunction after arsenic exposure including altered epigenetics; hippocampal function; glucocorticoid and hypothalamus-pituitary-adrenal axis (HPA) pathway signaling; glutamatergic, cholinergic and monoaminergic signaling; adult neurogenesis; and increased Alzheimer’s-associated pathologies. Finally, we briefly discuss new studies focusing on therapeutic strategies to combat arsenic toxicity including the use of selenium and zinc.

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“…However, the impact of arsenic on the epigenetic status of the brain has not been thoroughly investigated, particularly in the context of developmental exposure. To date, there have been three studies on the effects of developmental exposure to arsenic in the brain, suggesting an impact of arsenic on histone acetylation and DNA methylation with concurrent deficits in proteins that may underlie learning and memory deficits (Zarazua et al, 2010, Martinez et al, 2011, Cronican et al, 2013). Conversely, the literature on the effect of arsenic on the epigenome is quite extensive in the context of cancer (Ray et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain

Tyler

Hafez

Solomon

et al. 2015

Toxicology and Applied Pharmacology

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Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity alters the epigenome, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50 ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain. As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and expression of associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3 K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region- specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3 K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development induces alterations in the adult brain via histone modifications and chromatin modifiers a sex- and region-specific manner.

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Decreased arginine methylation and myelin alterations in arsenic exposed rats

Cited by 49 publications

References 55 publications

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

Carotid Intima-Media Thickness and Plasma Asymmetric Dimethylarginine in Mexican Children Exposed to Inorganic Arsenic

The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human and Rodent Studies: A Review

Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain

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