Research. Global Analysis of Posttranscriptional Gene Expression in Response to Sodium Arsenite.
Background: Inorganic arsenic species are potent environmental toxins and causes of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. Objectives: We evaluated the prevalence of changes in mRNA stability in respo...
| Publicado en: | Environmental Health Perspectives Vol. 123; no. 4; pp. 324 - 331 |
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| Autores principales: | , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
National Institute of Environmental Health Sciences
Apr2015
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=103790200&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 103790200 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00916765 3B5 jtl: Environmental Health Perspectives issn: 00916765 maglogo: N pubinfo: dt: Apr2015 vid: 123 iid: 4 pid: 56539 pub: National Institute of Environmental Health Sciences place: Research Triangle Park, North Carolina artinfo: ui: 103790200 102123098 10.1289/ehp.1408626 103790200 ppf: 324 ppct: 7 formats: fmt: @attributes: type: P tig: atl: Research. Global Analysis of Posttranscriptional Gene Expression in Response to Sodium Arsenite. aug: au: Lian-Qun Qiu Abey, Sarah Harris, Shawn Shah, Ruchir Gerrish, Kevin E. Blackshear, Perry J. affil: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA sug: subj: Gene Expression Arsenates Pharmacodynamics Descriptive Statistics Data Analysis Software Confidence Intervals Odds Ratio Arsenates Analysis Arsenates Adverse Effects ab: Background: Inorganic arsenic species are potent environmental toxins and causes of numerous health problems. Most studies have assumed that arsenic-induced changes in mRNA levels result from effects on gene transcription. Objectives: We evaluated the prevalence of changes in mRNA stability in response to sodium arsenite in human fibroblasts. Methods: We used microarray analyses to determine changes in steady-state mRNA levels and mRNA decay rates following 24-hr exposure to noncytotoxic concentrations of sodium arsenite, and we confirmed some of these changes using real-time reverse-transcription polymerase chain reaction (RT-PCR). Results: In arsenite-exposed cells, 186 probe set-identified transcripts were significantly increased and 167 were significantly decreased. When decay rates were analyzed after actinomycin D treatment, only 4,992 (9.1%) of probe set-identified transcripts decayed by > 25% after 4 hr. Of these, 70 were among the 353 whose steady-state levels were altered by arsenite, and of these, only 4 exhibited significantly different decay rates between arsenite and control treatment. Real-time RT-PCR confirmed a major, significant arsenite-induced stabilization of the mRNA encoding δ aminolevulinate synthase 1 (ALAS1), the rate-limiting enzyme in heme biosynthesis. This change presumably accounted for at least part of the 2.7-fold increase in steady-state ALAS1 mRNA levels seen after arsenite treatment. This could reflect decreases in cellular heme caused by the massive induction by arsenite of heme oxygenase mRNA (HMOX1; 68‑fold increase), the rate-limiting enzyme in heme catabolism. Conclusions: We conclude that arsenite modification of mRNA stability is relatively uncommon, but in some instances can result in significant changes in gene expression. Citation: Qiu LQ, Abey S, Harris S, Shah R, Gerrish KE, Blackshear PJ. 2015. Global analysis of posttranscriptional gene expression in response to sodium arsenite. Environ Health Perspect 123:324-330; http://dx.doi.org/10.1289/ehp.1408626 pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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