Abstract

Lead ions (Pb2+) are toxic industrial pollutants associated with chronic inflammatory diseases in humans and animals. Previously, we found that Pb2+ 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 Pb2+ 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 Pb2+ 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 Pb2+ (1 μM) significantly increased levels of COX-2 mRNA compared with cells treated with Pb2+ 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 Pb2+-induced reduction in DNMT3a mRNA. In addition, gene knockdown of DNMT3a with short hairpin RNA correlated with increased COX-2 mRNA induced by Pb2+. Our findings suggest Pb2+ ions induce COX-2 expression indirectly by reducing DNMT3a methylation of the COX-2 promoter via transcription factors Rb and E2F1.

Original languageEnglish
Pages (from-to)1024-1032
Number of pages9
JournalEnvironmental Toxicology
Volume30
Issue number9
DOIs
Publication statusPublished - Sep 1 2015

Fingerprint

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

Keywords

  • Cyclooxygenase-2
  • DNA methyltransferase 3a
  • Epidermal growth factor receptor
  • Lead

ASJC Scopus subject areas

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

Cite this

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 (Pb2+)-Induced Cyclooxygenase-2 gene. Environmental Toxicology, 30(9), 1024-1032. https://doi.org/10.1002/tox.21976

Function of DNA methyltransferase 3a in lead (Pb2+)-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.

In: Environmental Toxicology, Vol. 30, No. 9, 01.09.2015, p. 1024-1032.

Research output: Contribution to journalArticle

Tsai YT, Chang CM, Wang JY, Hou MF, Wang JM, Shiurba R et al. Function of DNA methyltransferase 3a in lead (Pb2+)-Induced Cyclooxygenase-2 gene. Environmental Toxicology. 2015 Sep 1;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 (Pb2+)-Induced Cyclooxygenase-2 gene. In: Environmental Toxicology. 2015 ; Vol. 30, No. 9. pp. 1024-1032.
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