Oxidative stress can activate the epidermal platelet-activating factor receptor

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Platelet-activating factor (1-alkyl-2-acetyl-glycerophosphocholine) is a lipid mediator that has been implicated in keratinocyte function and cutaneous inflammation. Keratinocytes both synthesize platelet-activating factor and express functional platelet-activating factor receptors linked to calcium mobilization. Oxidative stress to various cells including keratinocytes can also result in the mobilization of intracellular Ca2+, a known stimulus for platelet-activating factor biosynthesis. The ability of the epidermal platelet-activating factor receptors to modulate oxidant- induced signaling was investigated using a unique model system created by retrovital-mediated transduction of the platelet-activating factor receptor- negative epithelial cell line KB with the platelet-activating factor receptor. Treatment of KB cells with the lipid prooxidant tert-butyl hydroperoxide induced transient increases in intracellular Ca2+ in a concentration-dependent fashion. Expression of the platelet-activating factor receptor in KB cells lowered the threshold for tert-butyl hydroperoxide- induced Ca2+ flux by an order of magnitude (10 μM in control KB versus 1 μM in KB cells expressing the platelet-activating factor receptors) and increased the peak change in intracellular Ca2+ concentration in response to this lipid hydroperoxide. This augmentation of tert-butyl hydroperoxide- induced Ca2+ mobilization was inhibited by pretreatment with the two competitive platelet-activating factor receptor antagonists CV-6209 and WEB 2086, as well as by the antioxidants vitamin E and 1,1,3,3-tetramethyl-2- thiourea. KB cells synthesized platelet-activating factor and the platelet- activating factor receptor agonist 1-palmitoyl-2-acetyl-glycerophosphocholine in response to tert-butyl hydroperoxide treatment, suggesting the augmentation of oxidative stress-induced signaling seen in platelet- activating factor receptor-expressing cells was due in part to endogenous platelet-activating factor biosynthesis. These studies suggest involvement of the epidermal platelet-activating factor receptors in oxidant-mediated signaling.

Original languageEnglish (US)
Pages (from-to)279-283
Number of pages5
JournalJournal of Investigative Dermatology
Volume112
Issue number3
DOIs
StatePublished - Jan 1 1999

Keywords

  • Calcium
  • Mass spectrometry
  • Oxidative stress
  • Peroxides
  • Platelet- activating factor

ASJC Scopus subject areas

  • Dermatology

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