Oxidative stress is implicated in arsenic‐induced neural tube defects in chick embryos

Han, Zhongji; Song, Ge; Cui, Yi; Xia, Hong-Fei; Ma, Xu

doi:10.1016/j.ijdevneu.2011.06.006

Cited by 54 publications

(34 citation statements)

References 47 publications

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“…These results are similar to those from previous studies that showed iAs-induced structural malformations in the chick (Han et al 2011) and mouse embryo models (Chaineau et al 1990; Tabocova et al 1996). The iAs-induced malformations in mouse have also been shown to be associated with systems-level changes in gene expression (Robinson et al 2011).…”

Section: Discussionsupporting

confidence: 92%

Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Ahir

Sanders

Rager

et al. 2013

Environ Health Perspect

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Background: The biological mechanisms by which environmental metals are associated with birth defects are largely unknown. Systems biology–based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention.Objectives: First, we applied a novel computational approach to identify a prioritized biological pathway that associates metals with birth defects. Second, in a laboratory setting, we sought to determine whether inhibition of the identified pathway prevents developmental defects.Methods: Seven environmental metals were selected for inclusion in the computational analysis: arsenic, cadmium, chromium, lead, mercury, nickel, and selenium. We used an in silico strategy to predict genes and pathways associated with both metal exposure and developmental defects. The most significant pathway was identified and tested using an in ovo whole chick embryo culture assay. We further evaluated the role of the pathway as a mediator of metal-induced toxicity using the in vitro midbrain micromass culture assay.Results: The glucocorticoid receptor pathway was computationally predicted to be a key mediator of multiple metal-induced birth defects. In the chick embryo model, structural malformations induced by inorganic arsenic (iAs) were prevented when signaling of the glucocorticoid receptor pathway was inhibited. Further, glucocorticoid receptor inhibition demonstrated partial to complete protection from both iAs- and cadmium-induced neurodevelopmental toxicity in vitro.Conclusions: Our findings highlight a novel approach to computationally identify a targeted biological pathway for examining birth defects prevention.

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Section: Discussionsupporting

confidence: 92%

Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Ahir

Sanders

Rager

et al. 2013

Environ Health Perspect

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“…To further strengthen this, we show that the same in vitro / in vivo manipulations of MnSOD also ameliorate diabetes-induced increase in retinal Tet activity. Consistent with this, Tets are activated under high oxygen conditions by alpha ketoglutarate, a cofactor produced in the citric acid cycle [36], and N-acetyl-l-cysteine, a known antioxidant, diminishes global DNA hypomethylation [37]. …”

Section: Discussionmentioning

confidence: 96%

Role of oxidative stress in epigenetic modification of MMP-9 promoter in the development of diabetic retinopathy

Kowluru

Shan

2017

Graefes Arch Clin Exp Ophthalmol

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Background In the pathogenesis of diabetic retinopathy, damaged retinal mitochondria accelerate apoptosis of retinal capillary cells, and regulation of oxidative stress by manipulating mitochondrial superoxide dismutase (SOD2) protects mitochondrial homeostasis and prevents the development of diabetic retinopathy. Diabetes also activates matrix metalloproteinase-9 (MMP-9), and activated MMP-9 damages retinal mitochondria. Recent studies have shown a dynamic DNA methylation process playing an important role in regulation of retinal MMP-9 transcription in diabetes; the aim of this study is to investigate the role of oxidative stress in MMP-9 transcription. Methods The effect of regulation of mitochondrial superoxide on DNA methylation of MMP-9 promoter region was investigated in retinal endothelial cells incubated in the presence or absence of a MnSOD mimetic- MnTBAP, by quantifying the levels of 5 methyl cytosine (5mC) and hydroxyl-methyl cytosine (5hmC). The binding of DNA methylating, and of hydroxymenthylating enzymes (Dnmts and Tets, respectively), at MMP-9 promoter (by chromatin immunoprecipitation) was also evaluated. The in vitro results were confirmed in the retina of diabetic mice overexpressing SOD2. Results MnTBAP attenuated glucose-induced decrease in 5mC levels and increase on Dnmt1 binding at the MMP-9 promoter region. MnTBAP also ameliorated alterations in 5hmC levels and Tet binding, regulated MMP-9 transcription, and prevented mitochondrial damage. Similarly, mice overexpressing SOD2 were protected from diabetes-induced alteration in MMP-9 promoter methylation, and its transcription. Conclusions Thus, regulation of oxidative stress by pharmacologic/genetic approaches maintains retinal mitochondrial homeostasis by ameliorating epigenetic modifications in the MMP-9 promoter region.

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“…ventral body wall defects) were reported in embryos exposed in utero to cadmium [37]. Another study documented arsenic-induced altered expression of DNMTs and MBDs, a significant decrease in S-adenosylmethionine (SAM) (the source of the “methyl” group for DNA methylation), and global DNA hypomethylation - resulting in neural tube defects in exposed embryos [38]. …”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke induces proteasomal-mediated degradation of DNA methyltransferases and methyl CpG-/CpG domain-binding proteins in embryonic orofacial cells

Mukhopadhyay

Greene

Pisano

2015

Reproductive Toxicology

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Orofacial clefts, the most prevalent of developmental anomalies, occur with a frequency of 1 in 700 live births. Maternal cigarette smoking during pregnancy represents a risk factor for having a child with a cleft lip and/or cleft palate. Using primary cultures of first branchial arch-derived cells (1-BA cells), which contribute to the formation of the lip and palate, the present study addressed the hypothesis that components of cigarette smoke alter global DNA methylation, and/or expression of DNA methyltransferases (Dnmts) and various methyl CpG-binding proteins. Primary cultures of 1-BA cells, exposed to 80 μg/ml cigarette smoke extract (CSE) for 24 hrs, exhibited a >13% decline in global DNA methylation and triggered proteasomal-mediated degradation of Dnmts (DNMT-1, and - 3a), methyl CpG binding protein 2 (MeCP2) and methyl-CpG binding domain protein 3 (MBD-3). Pretreatment of 1-BA cells with the proteasomal inhibitor MG-132 completely reversed such degradation. Collectively, these data allow the suggestion of a potential epigenetic mechanism underlying maternal cigarette smoke exposure-induced orofacial clefting.

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Oxidative stress is implicated in arsenic‐induced neural tube defects in chick embryos

Cited by 54 publications

References 47 publications

Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Systems Biology and Birth Defects Prevention: Blockade of the Glucocorticoid Receptor Prevents Arsenic-Induced Birth Defects

Role of oxidative stress in epigenetic modification of MMP-9 promoter in the development of diabetic retinopathy

Cigarette smoke induces proteasomal-mediated degradation of DNA methyltransferases and methyl CpG-/CpG domain-binding proteins in embryonic orofacial cells

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