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 a...Continue Reading
References
Sep 1, 1996·Toxicology and Applied Pharmacology·P M Fernandez-SalgueroF J Gonzalez
Nov 1, 1996·The Journal of Biological Chemistry·R M KramerJ A Jakubowski
Jun 1, 1997·Chemistry & Biology·K P WilsonM S Su
May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·A S WeyrichG A Zimmerman
Oct 12, 2000·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·B H ShahS Arshad Saeed
Aug 8, 2001·The Journal of Cell Biology·S LindemannA S Weyrich
Feb 8, 2003·Biochimica Et Biophysica Acta·Junsei Mimura, Yoshiaki Fujii-Kuriyama
Sep 13, 2003·Chest·Lawrence F Brass
May 18, 2005·Oncogene·Carsten WeissMartin Göttlicher
Oct 26, 2005·Journal of Thrombosis and Haemostasis : JTH·E FalcinelliP Gresele
Aug 11, 2006·Journal of Thrombosis and Haemostasis : JTH·M GilardJ Boschat
Feb 27, 2007·Archives of Biochemistry and Biophysics·Christoph Franz Adam VogelFumio Matsumura
Apr 7, 2007·FEBS Letters·Robert BaroukiPedro M Fernandez-Salguero
Oct 16, 2007·Journal of Biochemical and Molecular Toxicology·Leslie M Tompkins, Andrew D Wallace
Feb 20, 2008·Chemico-biological Interactions·Pavla HenklováZdenek Dvorák
Jun 10, 2008·Trends in Pharmacological Sciences·Paolo GreseleStefania Momi
Sep 13, 2008·Journal of the American College of Cardiology·Edmund PezallaIndira Pulliadath
Oct 22, 2008·Archives of Biochemistry and Biophysics·Eric M SciulloFumio Matsumura
Nov 11, 2008·Biochemical Pharmacology·Fumio Matsumura
Dec 10, 2008·Biochemistry·Wen Li, Fumio Matsumura
Sep 29, 2009·Biochemical Pharmacology·Bin DongFumio Matsumura
Mar 17, 2010·Biochimie·Christina C LeslieMichael H Gelb
Jan 14, 2011·British Journal of Haematology·Stephan Lindsey, Eleftherios T Papoutsakis
Jul 20, 2011·The Journal of Pharmacology and Experimental Therapeutics·Binoy ShivannaBhagavatula Moorthy
Aug 11, 2012·The Journal of Pharmacology and Experimental Therapeutics·Un-Ho JinStephen Safe
Jan 15, 2014·Journal of Thrombosis and Haemostasis : JTH·S LindseyE T Papoutsakis
Jul 12, 2014·BMC Cancer·Un-Ho JinStephen Safe
Aug 19, 2014·Blood Cells, Molecules & Diseases·Seongcheol KimPudur Jagadeeswaran
Citations
Oct 27, 2016·Chemosphere·Tomasz MolcanRenata E Ciereszko
Aug 13, 2017·Stem Cells Translational Medicine·Nikoletta PsathaThalia Papayannopoulou
Jan 22, 2019·Spine·Kevin A SonnJohn J Callaci
Sep 2, 2020·Biology·George AndersonGianluigi Mazzoccoli
Oct 17, 2018·Toxins·Tawfik AddiStéphane Burtey
Feb 23, 2019·Archives of Toxicology·Nozomi FujisawaChiharu Tohyama
Feb 16, 2020·Scientific Reports·Ashley N SharpeJoshua A Stern
Dec 14, 2018·Frontiers in Physiology·Malgorzata KarbowskaDariusz Pawlak
Nov 16, 2019·European Journal of Medicinal Chemistry·Daniela DolciamiAntonio Macchiarulo
Jan 9, 2021·Frontiers in Cell and Developmental Biology·Yenan MoXusheng Liu
Dec 31, 2020·International Journal of Molecular Sciences·George Anderson
Mar 5, 2021·Frontiers in Immunology·Angela Rico de SouzaCarolyn J Baglole
Sep 25, 2021·Archives of Toxicology·Karl Walter Bock