Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...最新文献

{"title":"Lead-Induced Cell Cycle Arrest in Human Liver Carcinoma (HepG₂) Cells: Involvement of oxidative stress, p53 and <i>Cyclin</i> A.","authors":"Clement G Yedjou, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Recent studies in our laboratory have demonstrated that lead is cytotoxic to human liver carcinoma (HepG₂) cells, showing a 48 h-LD₅₀ of 35.5 ± 9.2ug/mL. However, its molecular mechanisms of toxicity are still largely unknown. Hence, the aim of the present study was to use HepG₂ cells as a test model to investigate the molecular mechanisms of lead-induced oxidative stress and modulation of cellular response proteins.</p><p><strong>Methods: </strong>To achieve this goal, we performed lipid peroxidation assay for malondialdehyde (MDA) determination, western blot and densitometric analyses for genes and related proteins expression in human liver carcinoma cells.</p><p><strong>Results: </strong>Data obtained from the lipid peroxidation assay demonstrated a significant increase (p ≤ 0.05) of MDA levels in lead-treated HepG₂ cells compared to control cells. Western Blot analysis showed a strong dose-response relationship with regard to p53 expression, and a significant repression in <i>cyclin A</i> in lead-treated cells.</p><p><strong>Conclusions: </strong>Findings from this research indicate that lead is able to cause oxidative stress, cell cycle arrest through activation of the 53-kDa tumor suppressor protein and down regulation of the <i>cyclin</i> A protein in human liver carcinoma (HepG₂) cells.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"11 ","pages":"242-246"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577017/pdf/nihms310486.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34098126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic Doses of Ascorbic Acid Increase Arsenic Trioxide Toxicity in Human Jurkat -T Lymphoma Cells.","authors":"Clement G Yedjou, Raven Byrd, Lacambrion Allen, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Arsenic trioxide (ATO) has been reported to have activity <i>in vitro</i> against multiple myeloma cells. Recently, it has also been used as a therapeutic agent to treat acute promyelocytic leukemia (APL) patients who have relapsed from conventional treatment with all-trans retinoic acid (ATRA) and chemotherapy. Recent studies from our laboratory indicate that ascorbic acid (AA) enhances the activity of ATO in HL-60 cells by increasing its cytotoxic effect and the level of oxidative stress. However, the potential effect of AA and ATO combination in the treatment of lymphoma patients has not been examined.</p><p><strong>Aim: </strong>Our central aim was to assess whether physiologic doses of ascorbic acid increase ATO toxicity in human Jurkat T lymphoma cells.</p><p><strong>Methods: </strong>Human Jurkat T lymphoma cells were treated either with a dose (9μg/mL) of ATO alone or with several physiologic doses of AA plus 9μg/mL ATO for 48 h. Cell survival was determined by trypan blue exclusion test using the Cellometer Vision.</p><p><strong>Results: </strong>Data generated from this experiment indicated that AA co-treatment at 100μM and 200μM significantly (<i>p</i> < 0.05) increased cell death in ATO-treated cells. The viability decreased from 61 ± 8% in cells with ATO alone to 31 ± 4% in cells treated with 200μM AA plus 9μg/mL ATO.</p><p><strong>Conclusions: </strong>Our research demonstrates that ATO alone is cytotoxic to human Jurkat T lymphoma cells, and co-administration of physiologic doses of AA enhances its toxicity in a dose-dependent manner.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"11 ","pages":"236-241"},"PeriodicalIF":0.0,"publicationDate":"2011-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4577053/pdf/nihms310499.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34201346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arsenic Trioxide Modulates DNA Synthesis and Apoptosis in Lung Carcinoma Cells.","authors":"Alice M Walker,&nbsp;Jacqueline J Stevens,&nbsp;Paul B Tchounwou","doi":"10.3390/ijerph7051996","DOIUrl":"https://doi.org/10.3390/ijerph7051996","url":null,"abstract":"<p><p>Arsenic is a heavy metal that is ubiquitous in the environment. The toxicity of arsenic depends upon its chemical form; the organic forms being usually less harmful than inorganic ones. The primary source of human exposure is through drinking water and food. Arsenic acts on cells through a variety of mechanisms, influencing numerous signal transduction pathways and resulting in a vast range of cellular effects that include apoptosis induction, growth inhibition, promotion or inhibition of differentiation, and angiogenesis inhibition. The primary objective of this research is to evaluate the effects of arsenic trioxide on DNA synthesis and to determine whether arsenic induces apoptosis via caspase activation and the activation the mitogen -activated protein kinase (MAPK) in lung carcinoma cells. To achieve this goal, the lung cancer (A549) cells were cultured following standard protocols, and exposed to various doses (0, 2, 4, 6, 8, and 10 mug/ml) of arsenic trioxide for 48 h with LC(50) being 7.8mug/ml. The proliferative response (DNA synthesis) to arsenic trioxide was determined by [(3)H] thymidine incorporation assay. Arsenic trioxide-induced apoptosis was determined by DNA laddering. Caspase -3 activation was assessed by the caspase-3 fluorescein isothiocyanate (FITC) assay. p38 MAP kinase activity was examined by immunoblot analysis using phospho p38 MAPK mab primary antibody in the presence of ATP and transcription factor (ATF-2) as a substrate. [(3)H] thymidine incorporation assay revealed biphasic reaction; showing cell proliferation at a lower level of exposure, and a dose-related cytotoxic response at higher levels of exposure in A549 cell line. Findings from the DNA laddering assay indicated that arsenic trioxide induced apoptosis in the lung carcinoma cells. Our findings revealed that arsenic trioxide modulated caspase 3 activity and induced p38 map kinase activation in lung carcinoma (A549) cells.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"7 5","pages":"1996-2007"},"PeriodicalIF":0.0,"publicationDate":"2010-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3390/ijerph7051996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28975223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Manganese Transport into the Brain: Putative Mechanisms.","authors":"Michael Aschner,&nbsp;Ana Paula Marreilha Dos Santos,&nbsp;Keith M Erikson,&nbsp;Wei Zheng","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>An important process in the toxicologic outcome of exposure to metals is their transport from plasma into the brain across the capillary endothelial cells that comprise the blood-brain barrier (BBB). The review, briefly delineates the known transport mechanisms of manganese (Mn) across the BBB, a crucial step in Mn accumulation in the brain. Herein, we discuss the distribution of Mn in the central nervous system (CNS) and identify putative transport mechanism for Mn, emphasize the close chemical interaction between Mn and iron (Fe) and the role of transferrin (Tf) and divalent metal transport1 (DMT1) in this process.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"695-700"},"PeriodicalIF":0.0,"publicationDate":"2008-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6309952/pdf/nihms-1001833.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36822366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Acetyl-cysteine Protection Against Lead-Induced Oxidative Stress and Genotoxicity in Human Liver Carcinoma (HepG₂) Cells.","authors":"Clement G Yedjou, Daren Waters, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The human liver carcinoma (HepG2) cells as well as other cell lines are particularly susceptible to oxidative damage, and it is therefore important to find agents that protect against this process. N-acetyl-cysteine (NAC) is the acetylated form of L-cysteine. It has an impressive list of protective effects including: antioxidant activity, decrease of the biologically effective dose of carcinogens, anti-inflammatory activity, immunological effects, inhibition of progression to malignancy and metastasis, and protection from the adverse effects of chemopreventive and chemotherapeutic agents. Previous studies in our laboratory have shown that lead nitrate induces cytotoxicity and oxidative stress to HepG₂ cells in a dose-dependent manner. In this research, we hypothesized that the antioxidant, n-acetyl-l-cysteine attenuates oxidative stress and genotoxicity, and thereby provides cellular protection against lead toxicity. To this hypothesis, we performed the thiobarbituric acid test for lipid peroxidation and the microgel electrophoresis (comet) assay for genotoxicity. The results generated from the thiobarbituric acid test showed a significant reduction of lipid peroxidation by-product (malondialdehyde) in HepG₂ cells co-exposed to NAC and lead nitrate compared to lead nitrate alone. Incubation of HepG₂ cells with increasing concentrations of NAC decreased the amount of MDA formation progressively in lead nitrate-treated HepG₂ cells. Data obtained from the comet assay indicated a strong dose-response relationship with regard to lead nitrate-induced genotoxic damage in HepG₂ cells. However, the addition of NAC <i>in vitro</i> showed a significant reduction (p < 0.05) in the comet tail length, percentage of DNA cleavage, comet tail moment, as well as comet tail arm respectively in cells co-treated with NAC and lead nitrate. Findings from these studies demonstrated that NAC inhibits malondialdehyde (MDA) production and genotoxicity in lead nitrate-treated HepG₂ cells in a dose-dependent manner. Under this <i>in vitro</i> condition, NAC was found to be effective in reducing MDA formation, cellular injury, and genotoxic damage in HepG₂ cells exposed to lead nitrate.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"419-424"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72212232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GENOTOXIC MECHANISMS OF ARSENIC TRIOXIDE IN HUMAN JURKAT T-LYMPHOMA CELLS.","authors":"Clement Yedjou, La'mont Sutton, Paul Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Arsenic trioxide (As(2)O(3)) has cytotoxic effects on several cancer cell lines. However, the molecular mechanisms of action remain to be elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by As(2)O(3) in a human Jurkat T-lymphoma cell line using the trypan blue exclusion test and alkaline single cell gel electrophoresis (Comet) assays, respectively. Jurkat T-cells were treated with different doses of As(2)O(3) for 24 and 48 h prior to cytogenetic assessment. Data obtained from the trypan blue exclusion test indicated that As(2)O(3) significantly (p < 0.05) reduced the viability of Jurkat T-cells in a dose and time-dependent manner. Data generated from the comet assay also indicated a significant dose and time-dependent increase in DNA damage in Jurkat T-cells associated with As(2)O(3) exposure. We observed a significant increase (P < 0.05) in comet tail-length, tail arm and tail moment, as well as in percentages of DNA cleavage at all doses tested, showing an evidence As(2)O(3) -induced genotoxic damage in Jurkat T-cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by heavy metals such as arsenic. Taken together, our findings suggest that As(2)O(3) exposure significantly (p < 0.05) reduces cellular viability and induces DNA damage in human Jurkat T-lymphoma cells.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"495-499"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3142934/pdf/nihms-310544.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30039001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxicity and oxidative stress in human liver carcinoma cells exposed to arsenic trioxide (HepG(2)).","authors":"Erika Brown, Clement G Yedjou, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Arsenic is a trace element that occurs naturally in the earth's crust. It has been found to be a major contaminant in groundwater supply in several countries of the world. Whether ingested or inhaled, arsenic induces both systemic (skin disorders, cardiovascular diseases, anemia, peripheral neuropathy, liver and kidney damage) and carcinogenic (skin, lung, bladder and liver neoplasms) effects. However, its molecular mechanisms of toxicity are not completely understood. In this research, we used HepG(2) cells as a model to study the cytotoxicity and oxidative stress associated with exposure to arsenic trioxide. We hypothesized that oxidative stress plays a role in arsenic trioxide induced cytotoxicity. To test this hypothesis, we performed both MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide] assay and trypan blue exclusion test for cell viability and the thiobarbituric acid test for lipid peroxidation. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HepG(2) cells, showing a LD(50) value of about 23 mug/mL upon 24 h of exposure, indicating a dose-dependent response. Similar trend was obtained with the trypan blue exclusion test. Data generated from the thiobarbituric acid test showed a significant increase (p </= 0.05) in MDA levels in arsenic trioxide-treated HepG(2) cells compared to control cells. Arsenic trioxide treatment significantly increased cellular content of reactive oxygen species (ROS), as evidenced by the increase in lipid peroxidation by-products. Taken together, these results indicate that arsenic trioxide is cytotoxic to HepG(2) cells. This cytotoxicity is mediated by oxidative stress, a biomarker of cellular injury.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"583-587"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2908498/pdf/nihms112988.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29143230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper-Induced Cytotoxicity and Transcriptional Activation of Stress Genes in Human Liver Carcinoma (HepG(2)) Cells.","authors":"Paul B Tchounwou, Cecilia Newsome, Joyce Williams, Konsuela Glass","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Copper is a naturally occurring element found as a component of many minerals. It is an essential nutrient that is normally present in a wide variety of tissues. In humans, ingestion of large quantities of copper salts may cause gastrointestinal, hepatic, and renal effects with symptoms such as severe abdominal pain, vomiting, diarrhea, hemolysis, hepatic necrosis, hematuria, proteinuria, hypotension, tachycardia, convulsions, coma, and death. The chronic toxicity of copper has been characterized in patients with Wilson's disease, a genetic disorder causing copper accumulation in tissues. Although the clinical manifestations of Wilson's disease (cirrhosis of the liver, hemolytic anemia, neurologic abnormalities, and corneal opacities) are known, the cellular and molecular events associated with copper toxicity are poorly understood. In the present study, we used human liver carcinoma (HepG(2)) cells as a model to study the cytotoxicity, and the potential mechanisms of copper-induced toxicity and carcinogenesis. We hypothesized that copper-induction of stress genes may play a role in the cellular and molecular events leading to toxicity and tumor formation in liver cells. To test this hypothesis, we performed the MTT-assay for cell viability, the CAT-Tox(L) assay for gene induction, to assess the transcriptional activation of stress genes. Data obtained from the MTT assay indicated a strong dose-response relationship with respect to copper toxicity. Upon 48 h of exposure, the chemical dose required to cause 50% reduction in cell viability (LD(50)) was computed to be 220.5 ± 23.8 μg/mL copper sulfate. The CAT-Tox (L) assay showed statistically significant inductions (p < 0.05) of a significant number of stress genes including c-fos, HMTIIA, HSP70, GRP78, RARE, GADD153, and RARE. These data support previous research indicating that copper overload is hepatotoxic. The CAT-Tox data on the other hand indicate that copper overload induces proteotoxic effects (HMTIIA, HSP70, GRP78), inflammatory reactions/oxidative stress (c-fos), and growth arrest and DNA damage (p53, GADD153). The induction of RARE points to its potential involvement in growth and development.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"285-290"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058949/pdf/nihms106197.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29757941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ASCORBIC ACID - MODULATION OF ARSENIC TRIOXIDE TOXICITY: IMPLICATION FOR THE CLINICAL TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA.","authors":"Clement G Yedjou, Erika Brown, Christian Rogers, Paul B Tchounwou","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Background: </strong>Acute Promyelocytic Leukemia (APL) is a subtype of acute leukemia which can affect people of any age. It strikes about 1,500 patients in the United States each year. Recent <i>in vitro</i> and <i>in vivo</i> studies have shown that arsenic trioxide (ATO) can induce clinical remission in <i>de-novo</i> and APL patients that have relapsed from conventional treatment. Ascorbic acid (AA) is an anti-oxidant and free radical scavenger effective against peroxyl- and hydroxyl-radicals, superoxide, singlet oxygen and peroxynitrite. Although research has shown that AA can prevent cancer by deactivating free radicals before they can damage DNA and initiate tumor growth, there are also published reports indicating that it may act as a pro-oxidant that helps the body's own free radical defense mechanism destroy tumors in their early stages.</p><p><strong>Aim: </strong>The aim of this research was to study the modulatory effect of AA on ATO-induced oxidative stress in leukemia cells.</p><p><strong>Methods: </strong>In the present investigation, we performed the MTT assay and trypan blue exclusion test for cell viability. We also performed the thiobarbituric acid test to determine the levels of malondialdehyde (MDA) production in HL-60 cells co-exposed to ascorbic acid (AA) and ATO.</p><p><strong>Results: </strong>The results of MTT assay indicated that AA exposure potentiates the cytotoxicity of ATO in HL-60 cells, as evidenced by a gradual increase in MDA levels with increasing doses of AA. From these results, we concluded that the addition of the ascorbic acid to ATO-treated HL-60 cells enhances the formation of reactive oxygen species (ROS).</p><p><strong>Conclusions: </strong>Based on these direct <i>in vitro</i> findings, our study provides evidence that AA may extend the therapeutic spectrum of ATO, and improve the clinical outcome associated with ATO monotherapy <i>in vivo</i>.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"413-418"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4634851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental arsenic as a disruptor of insulin signaling.","authors":"David S Paul, Vicenta Devesa, Araceli Hernandez-Zavala, Blakely M Adair, Felecia S Walton, Zuzana Drobnâ, David J Thomas, Miroslav Styblo","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Previous laboratory studies have shown that exposures to inorganic As (iAs) disrupt insulin production or glucose metabolism in cellular and animal models. Epidemiological evidence has also linked chronic human exposures to iAs to an increased risk of diabetes mellitus, a metabolic disease characterized by impaired glucose tolerance and insulin resistance. We have recently shown that arsenite and its methylated metabolites inhibit insulin-stimulated glucose uptake in cultured adipocytes by disrupting insulin-activated signal transduction pathway and preventing insulin-dependent translocation of GLUT4 transporters to the plasma membrane. Here, we present results of follow-up studies using male C57BL/6 mice chronically exposed to arsenite (1 to 50 ppm As) or to its metabolite methylarsonite (0.1 to 5 ppm As) in drinking water for 8 weeks. Results of these studies show that only the exposure to arsenite at the highest level of 50 ppm As produces symptoms attributable to impaired glucose tolerance. Notably, tissue concentrations of iAs and its methylated metabolites in pancreas and in major glucose metabolizing tissues in mice in this exposure group were comparable to the concentrations of total As reported in livers of Bangladeshi residents exposed to much lower concentrations of iAs in drinking water. These results suggest that because mice clear iAs and its metabolites more rapidly than humans, much higher exposure levels may be needed in mouse studies to produce the diabetogenic effects of iAs commonly found in human populations exposed to iAs from environmental sources.</p>","PeriodicalId":88934,"journal":{"name":"Metal ions in biology and medicine : proceedings of the ... International Symposium on Metal Ions in Biology and Medicine held ... = Les ions metalliques en biologie et en medecine : ... Symposium international sur les ions metalliques ...","volume":"10 ","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868343/pdf/nihms115163.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28987744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}