Exposures to subtoxic concentrations of iAs or MAs do not affect insulin signal mediators that regulate PIP levels in insulin-activated adipocytes

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> () Immunoblot analyses of the activated PI-3K, total PTEN, and phosphorylated PTEN (Ser380) in control 3T3-L1 adipocytes before or after activation with insulin and in insulin-activated adipocytes treated for 4 hr with 50 μM iAs or 2 μM MAs. Activated PI-3K was immunoprecipitated from control and exposed cells with an anti-phospho-Tyr (PY20) antibody and immunoblotted with an antibody against the regulatory (p85) subunit. Representative blots of three independent experiments are shown. () The ratio of phosphorylated PTEN (Ser380) to total PTEN expressed as a percent of the ratio found in control adipocytes before activation with insulin. Each value represents the mean ± SD; = 3 experiments

Exposures to subtoxic concentrations of iAs or MAs inhibit GLUT4 association with the plasma membrane of insulin-activated adipocytes

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> Immunofluorescent images of GLUT4 in plasma membrane lawns isolated from control (untreated) 3T3-L1 adipocytes before () and after activation () with insulin and from insulin-activated adipocytes treated for 4 hr with 50 μM iAs () or 2 μM MAs (). Adipocytes were fixed and sonicated to prepare plasma membrane lawns. GLUT4 was labeled with an anti-GLUT4 antibody and visualized with a fluorescent secondary antibody. Representative fields of two independent experiments are shown. Bars = 10 μm

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid-6

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid-8

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid-0

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p

Four-hour exposures to subtoxic concentrations of iAs or MAs do not increase DNA fragmentation in cultured adipocytes

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p> DNA fragmentation was measured by TUNEL in 3T3-L1 adipocytes treated with 50 μM iAs or 2 μM MAs for 4, 24, 48, and 72 hr. Untreated adipocytes were used as controls. Color images show green fluorescein signal of fragmented DNA in apoptotic cells. Gray-scale images illustrate the corresponding cell morphology. Representative fields of two independent experiments are shown. Bars = 40 μm

Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid-1

<p><b>Copyright information:</b></p><p>Taken from "Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid"</p><p></p><p>Environmental Health Perspectives 2007;115(5):734-742.</p><p>Published online 29 Jan 2007</p><p>PMCID:PMC1867998.</p><p>This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI</p

Additional file 1: of Biological and behavioral factors modify urinary arsenic metabolic profiles in a U.S. population

Supplemental Information. (DOCX 512 kb

Gut Microbiome Phenotypes Driven by Host Genetics Affect Arsenic Metabolism

Large individual differences in susceptibility to arsenic-induced diseases are well-documented and frequently associated with different patterns of arsenic metabolism. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that gut microbiome phenotypes affect the spectrum of metabolized arsenic species. However, it remains unclear how host genetics and the gut microbiome interact to affect the biotransformation of arsenic. Using an integrated approach combining 16S rRNA gene sequencing and HPLC-ICP-MS arsenic speciation, we demonstrate that IL-10 gene knockout leads to a significant taxonomic change of the gut microbiome, which in turn substantially affects arsenic metabolism

Gut Microbiome Perturbations Induced by Bacterial Infection Affect Arsenic Biotransformation

Exposure to arsenic affects large human populations worldwide and has been associated with a long list of human diseases, including skin, bladder, lung, and liver cancers, diabetes, and cardiovascular disorders. In addition, there are large individual differences in susceptibility to arsenic-induced diseases, which are frequently associated with different patterns of arsenic metabolism. Several underlying mechanisms, such as genetic polymorphisms and epigenetics, have been proposed, as these factors closely impact the individuals’ capacity to metabolize arsenic. In this context, the role of the gut microbiome in directly metabolizing arsenic and triggering systemic responses in diverse organs raises the possibility that perturbations of the gut microbial communities affect the spectrum of metabolized arsenic species and subsequent toxicological effects. In this study, we used an animal model with an altered gut microbiome induced by bacterial infection, 16S rRNA gene sequencing, and inductively coupled plasma mass spectrometry-based arsenic speciation to examine the effect of gut microbiome perturbations on the biotransformation of arsenic. Metagenomics sequencing revealed that bacterial infection significantly perturbed the gut microbiome composition in C57BL/6 mice, which in turn resulted in altered spectra of arsenic metabolites in urine, with inorganic arsenic species and methylated and thiolated arsenic being perturbed. These data clearly illustrated that gut microbiome phenotypes significantly affected arsenic metabolic reactions, including reduction, methylation, and thiolation. These findings improve our understanding of how infectious diseases and environmental exposure interact and may also provide novel insight regarding the gut microbiome composition as a new risk factor of individual susceptibility to environmental chemicals