Function of DNA methyltransferase 3a in lead (Pb 2+ )-Induced Cyclooxygenase-2 gene

Yao Ting Tsai, Che Mai Chang, Jaw Yuan Wang, Ming Feng Hou, Ju-Ming Wang, Robert Shiurba, Wen Chang Chang, Wei Chiao Chang

研究成果: Article

9 引文 (Scopus)

摘要

Lead ions (Pb 2+ ) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb 2+ ions induce COX-2 gene expression via the EGF receptor/nuclear factor-κB signal transduction pathway in epidermoid carcinoma cell line A431. In this study, to see whether Pb 2+ ions affect COX-2 expression by epigenetic mechanisms, we looked at the mRNAs of DNA methyltransferases (DNMTs) using real-time PCR of total RNA from these cells. Cells exposed to Pb 2+ had low levels of DNMT3a mRNA, whereas the levels of DNMT1 and DNMT3b mRNAs remained unchanged. Pretreatment of cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5 μM) followed by Pb 2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb 2+ alone. Overexpression of tumor suppressor gene Rb correlated with an increase in COX-2 mRNA and a decrease in DNMT3a mRNA. Conversely, overexpression of transcription factor E2F1 correlated with a decrease in COX-2 mRNA and an increase in DMNT3a mRNA. Pretreatment with EGFR inhibitors AG1478 and PD153035 significantly limited Pb 2+ -induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb 2+ . Our findings suggest Pb 2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1.

原文English
頁(從 - 到)1024-1032
頁數9
期刊Environmental Toxicology
30
發行號9
DOIs
出版狀態Published - 2015 九月 1

指紋

Cyclooxygenase 2
Genes
DNA
Messenger RNA
ion
gene
RNA
inhibitor
E2F1 Transcription Factor
Ions
methylation
tumor
gene expression
decitabine
Methyltransferases
Cells
Lead
DNA methyltransferase 3A
pollutant
animal

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Management, Monitoring, Policy and Law
  • Health, Toxicology and Mutagenesis

引用此文

Tsai, Y. T., Chang, C. M., Wang, J. Y., Hou, M. F., Wang, J-M., Shiurba, R., ... Chang, W. C. (2015). Function of DNA methyltransferase 3a in lead (Pb 2+ )-Induced Cyclooxygenase-2 gene Environmental Toxicology, 30(9), 1024-1032. https://doi.org/10.1002/tox.21976
Tsai, Yao Ting ; Chang, Che Mai ; Wang, Jaw Yuan ; Hou, Ming Feng ; Wang, Ju-Ming ; Shiurba, Robert ; Chang, Wen Chang ; Chang, Wei Chiao. / Function of DNA methyltransferase 3a in lead (Pb 2+ )-Induced Cyclooxygenase-2 gene 於: Environmental Toxicology. 2015 ; 卷 30, 編號 9. 頁 1024-1032.
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abstract = "Lead ions (Pb 2+ ) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb 2+ ions induce COX-2 gene expression via the EGF receptor/nuclear factor-κB signal transduction pathway in epidermoid carcinoma cell line A431. In this study, to see whether Pb 2+ ions affect COX-2 expression by epigenetic mechanisms, we looked at the mRNAs of DNA methyltransferases (DNMTs) using real-time PCR of total RNA from these cells. Cells exposed to Pb 2+ had low levels of DNMT3a mRNA, whereas the levels of DNMT1 and DNMT3b mRNAs remained unchanged. Pretreatment of cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5 μM) followed by Pb 2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb 2+ alone. Overexpression of tumor suppressor gene Rb correlated with an increase in COX-2 mRNA and a decrease in DNMT3a mRNA. Conversely, overexpression of transcription factor E2F1 correlated with a decrease in COX-2 mRNA and an increase in DMNT3a mRNA. Pretreatment with EGFR inhibitors AG1478 and PD153035 significantly limited Pb 2+ -induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb 2+ . Our findings suggest Pb 2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1.",
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Tsai, YT, Chang, CM, Wang, JY, Hou, MF, Wang, J-M, Shiurba, R, Chang, WC & Chang, WC 2015, ' Function of DNA methyltransferase 3a in lead (Pb 2+ )-Induced Cyclooxygenase-2 gene ', Environmental Toxicology, 卷 30, 編號 9, 頁 1024-1032. https://doi.org/10.1002/tox.21976

Function of DNA methyltransferase 3a in lead (Pb 2+ )-Induced Cyclooxygenase-2 gene . / Tsai, Yao Ting; Chang, Che Mai; Wang, Jaw Yuan; Hou, Ming Feng; Wang, Ju-Ming; Shiurba, Robert; Chang, Wen Chang; Chang, Wei Chiao.

於: Environmental Toxicology, 卷 30, 編號 9, 01.09.2015, p. 1024-1032.

研究成果: Article

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AU - Tsai, Yao Ting

AU - Chang, Che Mai

AU - Wang, Jaw Yuan

AU - Hou, Ming Feng

AU - Wang, Ju-Ming

AU - Shiurba, Robert

AU - Chang, Wen Chang

AU - Chang, Wei Chiao

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N2 - Lead ions (Pb 2+ ) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb 2+ ions induce COX-2 gene expression via the EGF receptor/nuclear factor-κB signal transduction pathway in epidermoid carcinoma cell line A431. In this study, to see whether Pb 2+ ions affect COX-2 expression by epigenetic mechanisms, we looked at the mRNAs of DNA methyltransferases (DNMTs) using real-time PCR of total RNA from these cells. Cells exposed to Pb 2+ had low levels of DNMT3a mRNA, whereas the levels of DNMT1 and DNMT3b mRNAs remained unchanged. Pretreatment of cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5 μM) followed by Pb 2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb 2+ alone. Overexpression of tumor suppressor gene Rb correlated with an increase in COX-2 mRNA and a decrease in DNMT3a mRNA. Conversely, overexpression of transcription factor E2F1 correlated with a decrease in COX-2 mRNA and an increase in DMNT3a mRNA. Pretreatment with EGFR inhibitors AG1478 and PD153035 significantly limited Pb 2+ -induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb 2+ . Our findings suggest Pb 2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1.

AB - Lead ions (Pb 2+ ) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb 2+ ions induce COX-2 gene expression via the EGF receptor/nuclear factor-κB signal transduction pathway in epidermoid carcinoma cell line A431. In this study, to see whether Pb 2+ ions affect COX-2 expression by epigenetic mechanisms, we looked at the mRNAs of DNA methyltransferases (DNMTs) using real-time PCR of total RNA from these cells. Cells exposed to Pb 2+ had low levels of DNMT3a mRNA, whereas the levels of DNMT1 and DNMT3b mRNAs remained unchanged. Pretreatment of cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5 μM) followed by Pb 2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb 2+ alone. Overexpression of tumor suppressor gene Rb correlated with an increase in COX-2 mRNA and a decrease in DNMT3a mRNA. Conversely, overexpression of transcription factor E2F1 correlated with a decrease in COX-2 mRNA and an increase in DMNT3a mRNA. Pretreatment with EGFR inhibitors AG1478 and PD153035 significantly limited Pb 2+ -induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb 2+ . Our findings suggest Pb 2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1.

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