TY - JOUR
T1 - Identification of platelet-activating factor acetylhydrolase II in human skin
AU - Marques, Mariangela
AU - Pei, Yong
AU - Southall, Michael D.
AU - Johnston, John M.
AU - Arai, Hiroyuki
AU - Aoki, Junken
AU - Inoue, Takao
AU - Seltmann, Holger
AU - Zouboulis, Christos C.
AU - Travers, Jeffrey B.
N1 - Funding Information:
The authors wish to acknowledge the technical assistance of Drs Silvio Marques and Dan Spandau (I.U. Department Dermatology). These studies are supported in part by grants from the Showalter Memorial Fundation, the Riley Memorial Association, and the National Institutes of Health grants AR1993 and HL62996. M.M. was supported by Brazilian grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo- FAPESP. M.S. was supported by a grant from the Dermatology Foundation. H.S. was supported by a grant from the Bundesinstitut für gesundheitlichen Verbraucherschutz und Veterinärmedizin (BgVV Z 5.1-1328-156).
PY - 2002/10
Y1 - 2002/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Keratinocytes
KW - Oxidative stress
KW - Platelet-activating factor
KW - Platelet-activating factor acetylhydrolase
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U2 - 10.1046/j.1523-1747.2002.01859.x
DO - 10.1046/j.1523-1747.2002.01859.x
M3 - Article
C2 - 12406338
AN - SCOPUS:18744403354
VL - 119
SP - 913
EP - 919
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 4
ER -