Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage

Gopal K. Marathe, Christopher Johnson, Steven D. Billings, Michael D. Southall, Yong Pei, Dan Spandau, Robert C. Murphy, Guy A. Zimmerman, Thomas M. McIntyre, Jeffrey Travers

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Ultraviolet B light (UVB) causes cutaneous inflammation and cell death, but the agents responsible are not defined. These studies examined the role of the platelet-activating factor (PAF) signaling system in UVB-mediated effects. Expression of the PAF receptor in the PAF receptor-negative epidermoid cell line KB augmented apoptosis in response to UVB irradiation. Overexpression of the PAF receptor in primary human keratinocytes also enhanced UVB-mediated apoptosis in vitro, and it enhanced apoptosis in an in vivo model of human keratinocytes grafted onto severe combined immune-deficient (SCID) mice. To define the mechanism by which UVB activates the PAF receptor, we used mass spectrometry to demonstrate significant amounts of the C4 PAF analogs 1-alkyl-2-(butanoyl and butenoyl)-sn-glycero-3-phosphocholine, as well as native PAF in an epidermal cell line after UVB irradiation. Supplementing the cells with the precursor phospholipid 1-hexadecyl-2-arachidonoyl-sn-glycero-3- phosphocholine (HAPC) increased the amount of C4 PAF analogs recovered after UVB exposure. We irradiated HAPC directly and found, even in the absence of a photosensitizer, fragmentation to C4-PAF receptor ligands. We conclude UVB photo-oxidizes cellular phospholipids, creating PAF analogs that stimulate the PAF receptor to induce further PAF synthesis and apoptosis. PAF signaling may participate in the cutaneous inflammation that occurs during photo-aggravated dermatoses.

Original languageEnglish
Pages (from-to)35448-35457
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number42
DOIs
StatePublished - Oct 21 2005

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Platelet Activating Factor
Ultraviolet Rays
Phospholipids
Radiation
Skin
Apoptosis
Keratinocytes
Cells
Irradiation
Inflammation
Cell Line
Photosensitizing Agents
Phosphorylcholine
Cell death
Skin Diseases
Mass spectrometry
platelet activating factor receptor
Mass Spectrometry
Cell Death
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage. / Marathe, Gopal K.; Johnson, Christopher; Billings, Steven D.; Southall, Michael D.; Pei, Yong; Spandau, Dan; Murphy, Robert C.; Zimmerman, Guy A.; McIntyre, Thomas M.; Travers, Jeffrey.

In: Journal of Biological Chemistry, Vol. 280, No. 42, 21.10.2005, p. 35448-35457.

Research output: Contribution to journalArticle

Marathe, GK, Johnson, C, Billings, SD, Southall, MD, Pei, Y, Spandau, D, Murphy, RC, Zimmerman, GA, McIntyre, TM & Travers, J 2005, 'Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage', Journal of Biological Chemistry, vol. 280, no. 42, pp. 35448-35457. https://doi.org/10.1074/jbc.M503811200
Marathe, Gopal K. ; Johnson, Christopher ; Billings, Steven D. ; Southall, Michael D. ; Pei, Yong ; Spandau, Dan ; Murphy, Robert C. ; Zimmerman, Guy A. ; McIntyre, Thomas M. ; Travers, Jeffrey. / Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 42. pp. 35448-35457.
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