Effect of Arsenic Exposure on NRF2-KEAP1 Pathway and Epigenetic Modification.

2.50
Hdl Handle:
http://hdl.handle.net/10146/618195
Title:
Effect of Arsenic Exposure on NRF2-KEAP1 Pathway and Epigenetic Modification.
Authors:
Janasik, Beata ( 0000-0002-0904-9869 ) ; Reszka, Edyta ( 0000-0003-2153-4864 ) ; Stanislawska, Magdalena; Jablonska, Ewa ( 0000-0002-3946-3964 ) ; Kuras, Renata ( 0000-0003-3424-5105 ) ; Wieczorek, Edyta ( 0000-0002-4390-2042 ) ; Malachowska, Beata; Fendler, Wojciech; Wasowicz, Wojciech ( 0000-0002-2991-9040 )
Abstract:
Arsenic (As) is a known toxic element and carcinogen. Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant genes in response to redox stress. To explore associations between As level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 61 occupationally exposed men with median (Me) age 50 years (interquartile range (IQR) 42-54) and in a control group of 52 men aged 40 (IQR 31-51.5) without occupational exposure. NRF2, KEAP1, GSTP1, HMOX1, NQO1, PRDX1, and TXNRD1 transcript levels were determined by means of quantitative real-time PCR along with the gene expression, methylation of NRF2 and KEAP1, as well as global DNA methylation were assessed. The median urine As tot. level in the exposed and control group was found to be 21.8 μg/g creat. (IQR 15.5-39.8 μg/g creat.) and 3.8 μg/g creat. (IQR 2.5-9.3) (p < 0.001). Global DNA methylation was significantly higher in occupationally exposed workers than in controls (Me 14.1 (IQR 9.5-18.1) vs Me 8.5 (IQR 5.9-12.6) p < 0.0001). NRF2 mRNA level was positively correlated with expression of all investigated NRF2-target genes in both groups (0.37 > R < 0.76, all p values < 0.0001). The multivariate linear regression adjusting for global methylation showed that As(III) level was significantly associated with expression of TXNRD1, GSTP1, HMOX1, and PRDX1. The results of this study indicate that arsenic occupational exposure is positively associated with global DNA methylation. The findings provide evidence for rather inactivation of NRF2-KEAP1 pathway in response to chronic arsenic exposure.
Affiliation:
Nofer Institute of Occupational Medicine, Lodz, Poland
Citation:
Biol Trace Elem Res (2017)
Journal:
Biological Trace Element Research
Issue Date:
15-Dec-2017
URI:
http://hdl.handle.net/10146/618195
DOI:
10.1007/s12011-017-1219-4
PubMed ID:
29247444
Additional Links:
https://link.springer.com/article/10.1007%2Fs12011-017-1219-4
Type:
Article
Language:
en
ISSN:
1559-0720
Sponsors:
This work was supported by the Grant for Scientific Research (2012/07/B/NZ7/04257) of the National Center of Sciences and the internal grant IMP 1.20 from the statutory activity resources of the Nofer Institute of Occupational Medicine in Lodz.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorJanasik, Beataen
dc.contributor.authorReszka, Edytaen
dc.contributor.authorStanislawska, Magdalenaen
dc.contributor.authorJablonska, Ewaen
dc.contributor.authorKuras, Renataen
dc.contributor.authorWieczorek, Edytaen
dc.contributor.authorMalachowska, Beataen
dc.contributor.authorFendler, Wojciechen
dc.contributor.authorWasowicz, Wojciechen
dc.date.accessioned2018-01-08T13:18:22Z-
dc.date.available2018-01-08T13:18:22Z-
dc.date.issued2017-12-15-
dc.identifier.citationBiol Trace Elem Res (2017)en
dc.identifier.issn1559-0720-
dc.identifier.pmid29247444-
dc.identifier.doi10.1007/s12011-017-1219-4-
dc.identifier.urihttp://hdl.handle.net/10146/618195-
dc.description.abstractArsenic (As) is a known toxic element and carcinogen. Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant genes in response to redox stress. To explore associations between As level and NRF2-regulated cytoprotective genes expression, an observational study was conducted in a population of 61 occupationally exposed men with median (Me) age 50 years (interquartile range (IQR) 42-54) and in a control group of 52 men aged 40 (IQR 31-51.5) without occupational exposure. NRF2, KEAP1, GSTP1, HMOX1, NQO1, PRDX1, and TXNRD1 transcript levels were determined by means of quantitative real-time PCR along with the gene expression, methylation of NRF2 and KEAP1, as well as global DNA methylation were assessed. The median urine As tot. level in the exposed and control group was found to be 21.8 μg/g creat. (IQR 15.5-39.8 μg/g creat.) and 3.8 μg/g creat. (IQR 2.5-9.3) (p < 0.001). Global DNA methylation was significantly higher in occupationally exposed workers than in controls (Me 14.1 (IQR 9.5-18.1) vs Me 8.5 (IQR 5.9-12.6) p < 0.0001). NRF2 mRNA level was positively correlated with expression of all investigated NRF2-target genes in both groups (0.37 > R < 0.76, all p values < 0.0001). The multivariate linear regression adjusting for global methylation showed that As(III) level was significantly associated with expression of TXNRD1, GSTP1, HMOX1, and PRDX1. The results of this study indicate that arsenic occupational exposure is positively associated with global DNA methylation. The findings provide evidence for rather inactivation of NRF2-KEAP1 pathway in response to chronic arsenic exposure.en
dc.description.sponsorshipThis work was supported by the Grant for Scientific Research (2012/07/B/NZ7/04257) of the National Center of Sciences and the internal grant IMP 1.20 from the statutory activity resources of the Nofer Institute of Occupational Medicine in Lodz.en
dc.language.isoenen
dc.relation.urlhttps://link.springer.com/article/10.1007%2Fs12011-017-1219-4en
dc.rightsArchived with thanks to Biological trace element researchen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/*
dc.subjectarsenicen
dc.subjectNrf2en
dc.subjectKEAP1en
dc.subjectgene expressionen
dc.titleEffect of Arsenic Exposure on NRF2-KEAP1 Pathway and Epigenetic Modification.en
dc.typeArticleen
dc.contributor.departmentNofer Institute of Occupational Medicine, Lodz, Polanden
dc.identifier.journalBiological Trace Element Researchen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in ECNIS-NIOM are protected by copyright, with all rights reserved, unless otherwise indicated.