Publikationsserver der Universitätsbibliothek Marburg

Titel:Expressionsanalyse der nukleären Rezeptoren PPAR-α/γ-1/γ-2 und der Transkriptionsfaktoren T-bet und GATA-3 nach Stimulation von dermalen Endothelzellen mit den Weichmacher, Di(2-ethylhexyl)phthalat-Metaboliten 2-Ethylhexanol und 4-Heptanon
Autor:Dutescu, Ralf Michael
Weitere Beteiligte: Wahl, H. G. (Prof. Dr. Dr.)
Veröffentlicht:2011
URI:https://archiv.ub.uni-marburg.de/diss/z2011/0342
URN: urn:nbn:de:hebis:04-z2011-03420
DOI: https://doi.org/10.17192/z2011.0342
DDC: Medizin
Titel (trans.):Expression analysis of nuclear receptors PPAR-α/γ-1/ γ -2 and transcription factors T-bet and GATA-3 after exposure to platiziser Di(2-ethylhexyl) phthalate methabolites 2-Ethylhexanol und 4-Heptanon in dermal microvascular endothelial cells
Publikationsdatum:2011-04-29
Lizenz:https://rightsstatements.org/vocab/InC-NC/1.0/

Dokument

Schlagwörter:
Weichmacher, GATA-3, DOP, DOP, T-bet

Zusammenfassung:
Hintergrund: Di(2-ethylhexyl) phthalate (DEHP) als Weichmacher aus der Familie der Phthalate ist bekannt für seinen schädlichen Einfluss auf Organe wie Herz, Leber und die Geschlechtsorgane. Im Gegensatz zu anderen Weichmachern bildet ausschließlich DEHP die Metabolite 2-Ethylhexanol (2EH) und 4-Heptanon (4HP), welchen eigene toxische Wirkungen zugeschrieben werden. Die Biodistribution des DEHP und seiner Metabolite über das kardiovaskuläre System, hat uns veranlaßt das Expressionsverhalten von nukleären Rezeptoren in mikrovaskulären Endothelzellen nach Stimulation durch 2EH und 4HP zu untersuchen. Methoden: MEHC1 Zellen wurden kultiviert und über 24 Stunden mit aufsteigenden Konzentrationen von 2-EH (500, 1000, 2000μg/ml) und 4-HP (250, 500, 1000, 2000μg/ml) inkubiert und anschließend nach RNA isolation für real-time PCR herangezogen. Die Expression der Transkriptionsfaktoren PPAR-α, γ-1, γ -2, T-bet und GATA-3 wurde relativ quantifiziert. Dabei wurde die Expression der unterschiedlich stimulierten Proben in Bezug zu einer unstimulierten Zellreihe untersucht. Ergebnisse: Die Untersuchungen zeigen eine Inhibition des an PPAR-α,-γ- 1 und γ -2 nach 2-EH Exposition (500, 1000 μg/ml) sowie Hochregulation des PPAR-α und Herabregulation des PPAR γ-1 und γ -2 in 4-HP (500, 1000 μg/ml) inkubierten Zellen. GATA-3 wird durch 2-ETH als auch durch 4-HP in allen Konzentrationen stimuliert. Die 2000 μg/ml Konzentration von 2-EH und 4HP ergab geringe cDNA Level, welches auf eine erhöte Zelltod hinweist. T-bet war in den Proben in Spuren nachweisbar. Diskussion: PPAR-α und –γ werden vasodillatatorische Effekte zugeschrieben. Unter Stimulation mit 2-EH bzw. 4-HP zeigen sich gegenläufige Einflüsse auf die PPAR-Expression und somit auf den Gefäßtonus. GATA-3-Expression wird im Zusammenhang mit der VCAM vermittelten Extravasion von Entzündngszellen gesehen. Auch hier zeigen sich antagonistische Einflüsse des 2EH gegenüber dem 4HP. In Zukünft könnten letztlich nur in-vivo Toxizitätsuntersuchungen abschliessend klären, welcher Einfluß sich aus dem gemeinsamen Auftreten der Metabolite ergibt. Zusammengenommen unterstützen die Ergebnisse jedoch die geforderte Einschränkung des DEHP- Gebrauchs.

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