Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor.

Ambrosio, Giuseppe; Oriente, Alfonso; Napoli, Claudio; Palumbo, Giuseppe; Chiariello, Paola; Marone, Gianni; Condorelli, M; Chiariello, Massimo; Triggiani, Massimo

doi:10.1172/jci117248

Cited by 137 publications

(68 citation statements)

References 73 publications

(70 reference statements)

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“…One possibility is that UVB could have inhibitory effects on PAF-acetylhydrolase enzymes. Indeed, oxidative stress has been reported to inactivate these enzymes that serve to degrade PAF and short-chained sn-2 glycerophosphocholines (44). A second possibility is that UVB is activating the PAF-R directly.…”

Section: Discussionmentioning

confidence: 99%

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

Dy¹,

Pei²,

Travers³

1999

Journal of Biological Chemistry

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Ultraviolet B radiation (UVB) has been shown to damage human keratinocytes in part by inducing oxidative stress and cytokine production. Indeed, UVB-induced production of the pro-inflammatory and cytotoxic cytokine tumor necrosis factor ␣ (TNF-␣) has been implicated in the epidermal damage seen in response to acute solar radiation. Though the lipid mediator platelet-activating factor (PAF) is synthesized in response to oxidative stress, and keratinocytes express PAF receptors linked to cytokine biosynthesis, it is not known whether PAF is involved in UVB-induced epidermal cell cytokine production. These studies examined the role of the PAF system in UVB-induced epidermal cell TNF-␣ biosynthesis using a novel model system created by retroviralmediated transduction of the PAF receptor-negative human epidermal cell line KB with the human PAF receptor (PAF-R). Treatment of PAF-R-expressing KB cells with the metabolically stable PAF-R agonist carbamoyl-PAF resulted in increased TNF-␣ mRNA and protein, indicating that activation of the epidermal PAF-R was linked to TNF-␣ production. UVB irradiation of PAF-R-expressing KB cells resulted in significant increases in both TNF-␣ mRNA and protein in comparison to UVB-treated control KB cells. However, UVB treatment up-regulated cyclooxygenase-2 mRNA levels to the same extent in both PAF-R-expressing and control KB cells. Pretreatment with the antioxidant vitamin E or the PAF-R antagonists WEB 2086 and A-85783 inhibited UVB-induced TNF-␣ production in the PAF-R-positive but not control KB cells. These studies suggest that the epidermal PAF-R may be a pharmacological target for UVB in skin.

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Section: Discussionmentioning

confidence: 99%

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

Dy¹,

Pei²,

Travers³

1999

Journal of Biological Chemistry

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“…The increase in biological activity of oxidatively modified DFP * LDL we observe may be attributable to an increase in the amount of biologically active phospholipids, due to the loss of the initial hydrolytic activity provided by LDL-associated PAF-AH. It has previously been shown that oxidation depletes LDL of PAF hydrolytic activity (24,48,49).…”

Section: Discussionmentioning

confidence: 99%

Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.

Watson¹,

Navab²,

Hama³

et al. 1995

J. Clin. Invest.

383

242

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Mildly oxidized low density lipoprotein (MM-LDL) HPLC analysis also revealed that the active oxidized phospholipid species in MM-LDL had been destroyed after PAF-AH treatment. In addition, treatment of MM-LDL with albumin removed polar phospholipids that, when reisolated, induced monocyte binding to endothelial cells. These polar phospholipids, when treated with PAF-AH, lost biological activity and were no longer detected by HPLC. These results suggest that PAF-AH in HDL protects against the production and activity of MM-LDL by facilitating hydrolysis of active oxidized phospholipids to lysolipids, thereby destroying the biologically active lipids in MM-LDL. (J. Clin. Invest. 1995. 95:774-782)

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“…This has two implications. First, active oxygen species and oxidants are inhibitors of PAF acetylhydrolase (54). Second, the generation of these active oxygen species can lead to the formation of proinflammatory, oxidatively fragmented phospholipids, which also are degraded by PAF acetylhydrolase (55,56).…”

Section: Figurementioning

confidence: 99%

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

Stafforini¹,

Numao²,

Tsodikov³

et al. 1999

J. Clin. Invest.

119

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Asthma, a family of airway disorders characterized by airway inflammation, has an increasing incidence worldwide. Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma. Its proinflammatory actions are antagonized by PAF acetylhydrolase. A missense mutation (V279F) in the PAF acetylhydrolase gene results in the complete loss of activity, which occurs in 4% of the Japanese population. We asked if PAF acetylhydrolase deficiency correlates with the incidence and severity of asthma in Japan. We found that the prevalence of PAF acetylhydrolase deficiency is higher in Japanese asthmatics than healthy subjects and that the severity of this syndrome is highest in homozygous-deficient subjects. We conclude that the PAF acetylhydrolase gene is a modulating locus for the severity of asthma. J. Clin. Invest. 103:989-997

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Oxygen radicals inhibit human plasma acetylhydrolase, the enzyme that catabolizes platelet-activating factor.

Abstract: Platelet-activating factor (PAF) can exert profound inflammatory

Cited by 137 publications

References 73 publications

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

Augmentation of Ultraviolet B Radiation-induced Tumor Necrosis Factor Production by the Epidermal Platelet-activating Factor Receptor

Effect of platelet activating factor-acetylhydrolase on the formation and action of minimally oxidized low density lipoprotein.

Deficiency of platelet-activating factor acetylhydrolase is a severity factor for asthma

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