Induction of human prostaglandin endoperoxide H synthase-2 (PHS-2) mRNA by TCDD.
Numerous transcription response elements (e.g. AP-1, AP-2, GRE, CREB, as well as DRE) have been identified in the transcription regulation region of the PHS-2 gene in both mouse and human. The discovery of a DRE in the region raised the possibility that PHS-2 could be induced by TCDD, a dioxin compound. The time course and dose dependence of TCDD induction of PHS-2 mRNA expression were observed in HUVEC, primary human epithelial cells. In the observed time range (0-24 hours) the steady-state mRNA expression levels of PHS-2, as well as of mRNA for CYP1A1, increased with time at a TCDD dose of 20 nM. At the 24 hour time point, TCDD-treated cells displayed significant dose-dependent elevation of PHS-2 over the range of 0-40 nM TCDD. The increases in PHS-2 mRNA in both the time course and dose dependence experiments were consistent with that of CYP1A1. In contrast, mRNA for PHS-1, the constitutively expressed isoform of PHS, did not show significant changes under the conditions tested. These results are the first to indicate that TCDD can elevate PHS-2 mRNA level in a time and dose dependent manner. Further work needs to be done to learn the molecular mechanism of activation of PHS-2 by TCDD and the relation of TCDD action with other regulatory factors in the control of PHS-2 expression.
Liu
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Department of Pharmacology University of Michigan, Ann Arbor 48109-0632, USA.
Levy
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Weber
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D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects* / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D019363:Cytochrome P-450 CYP1A1; D011451:Prostaglandin-Endoperoxide Synthases