TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway

Mónica Pombo, Michael W. Lamé, Naomi J. Walker, Danh H. Huynh, Fern Tablin

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The role of the aryl hydrocarbon receptor (AhR) in hemostasis has recently gained increased attention. Here, we demonstrate, by qRT-PCR and western blot, that human platelets express both AhR mRNA and AhR protein. AhR protein levels increase in a dose dependent manner when incubated with either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or omeprazole. Treatment of platelets with puromycin blocks increased AhR protein synthesis in the presence of AhR activators. Additionally, treatment of platelets with either activator results in phosphorylation of p38MAPK and cPLA2, two key signaling molecules in platelet activation pathways. Using the AhR competitive inhibitors alpha naphthoflavone and CH-223191, we show that phosphorylation of p38MAPK is AhR dependent. Further, inhibition of p38MAPK blocks downstream cPLA2 phosphorylation induced by TCDD or omeprazole. Treatment with AhR activators results in platelet priming, as demonstrated by increased platelet aggregation, which is inhibited by AhR antagonists. Our data support a model of the platelet AhR non-genomic pathway in which treatment with AhR activators results in increased expression of the AhR, phosphorylation of p38MAPK and cPLA2, leading to platelet priming in response to agonist.

Original languageEnglish (US)
Pages (from-to)28-36
Number of pages9
JournalToxicology Letters
Volume235
Issue number1
DOIs
StatePublished - May 9 2015
Externally publishedYes

Keywords

  • AhR non-genomic pathway
  • CPLA
  • P38MAPK
  • Platelet priming
  • Platelet signaling

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway'. Together they form a unique fingerprint.

  • Cite this