Identification of platelet-activating factor acetylhydrolase II in human skin

Mariangela Marques, Yong Pei, Michael D. Southall, John M. Johnston, Hiroyuki Arai, Junken Aoki, Takao Inoue, Holger Seltmann, Christos C. Zouboulis, Jeffrey Travers

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Platelet-activating factor acetylhydrolases are a family of specialized phospholipase A2 enzymes. They serve an anti-inflammatory function by converting the proinflammatory autocoid, PAF, into biologically inactive lyso-PAF, by the removal of the sn-2 acetyl group of this glycerophospholipid. Similarly, platelet-activating factor acetylhydrolases can also degrade oxidatively modified sn-2 polyunsaturated-fatty-acid-containing phospholipids, which are toxic to cells. Platelet-activating factor acetylhydrolase II is a recently cloned member of this family of specialized phospholipases. Consistent with a potential role of this intracellular enzyme in protecting membrane phospholipids against oxidative stress, platelet-activating factor acetylhydrolase II has been shown to translocate from cytosol to membranes in response to pro-oxidative stressors, and overexpression of this enzyme decreases the cytotoxic effects of these agents. The objective of this study was to assess whether platelet-activating factor acetylhydrolase II is involved in protecting skin against oxidative stress. Platelet-activating factor acetylhydrolase II protein was demonstrated in human skin by immunohistochemistry, with the highest levels of the enzyme found in sebaceous glands and lesser amounts in epidermal keratinocytes. Treatment of epidermal cells with t-butyl-hydroperoxide or ultraviolet B radiation resulted in platelet-activating factor acetylhydrolase II translocation from cytosol to membranes. To assess the role of this enzyme in epidermal function, a recombinant retroviral strategy was used to overexpressplatelet-activating factor acetylhydrolase II in the human keratinocyte-derived cell line HaCaT. Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apoptosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation. Similar levels of apoptosis, however, were seen in both control and platelet-activating-factor-acetylhydrolase-II-overexpressing HaCaT cells in response to C2 ceramide. These studies demonstrate the presence of platelet-activating factor acetylhydrolase II in a restricted pattern in human skin, and provide evidence that this specialized phospholipase is involved in protecting this organ against oxidative stress through the degradation of oxidatively modified bioactive phospholipids.

Original languageEnglish
Pages (from-to)913-919
Number of pages7
JournalJournal of Investigative Dermatology
Volume119
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Platelet Activating Factor
Skin
Oxidative stress
Enzymes
tert-Butylhydroperoxide
Phospholipids
Oxidative Stress
Phospholipases
Membranes
Keratinocytes
Cytosol
Cells
Radiation
Apoptosis
Glycerophospholipids
Sebaceous Glands
Poisons
Phospholipases A2
Cytotoxins
Unsaturated Fatty Acids

Keywords

  • Apoptosis
  • Keratinocytes
  • Oxidative stress
  • Platelet-activating factor
  • Platelet-activating factor acetylhydrolase

ASJC Scopus subject areas

  • Dermatology

Cite this

Identification of platelet-activating factor acetylhydrolase II in human skin. / Marques, Mariangela; Pei, Yong; Southall, Michael D.; Johnston, John M.; Arai, Hiroyuki; Aoki, Junken; Inoue, Takao; Seltmann, Holger; Zouboulis, Christos C.; Travers, Jeffrey.

In: Journal of Investigative Dermatology, Vol. 119, No. 4, 2002, p. 913-919.

Research output: Contribution to journalArticle

Marques, M, Pei, Y, Southall, MD, Johnston, JM, Arai, H, Aoki, J, Inoue, T, Seltmann, H, Zouboulis, CC & Travers, J 2002, 'Identification of platelet-activating factor acetylhydrolase II in human skin', Journal of Investigative Dermatology, vol. 119, no. 4, pp. 913-919. https://doi.org/10.1046/j.1523-1747.2002.01859.x
Marques, Mariangela ; Pei, Yong ; Southall, Michael D. ; Johnston, John M. ; Arai, Hiroyuki ; Aoki, Junken ; Inoue, Takao ; Seltmann, Holger ; Zouboulis, Christos C. ; Travers, Jeffrey. / Identification of platelet-activating factor acetylhydrolase II in human skin. In: Journal of Investigative Dermatology. 2002 ; Vol. 119, No. 4. pp. 913-919.
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