Advertisement

Research Article Free access | 10.1172/JCI117248

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

G Ambrosio, A Oriente, C Napoli, G Palumbo, P Chiariello, G Marone, M Condorelli, M Chiariello, and M Triggiani

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Ambrosio, G. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Oriente, A. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Napoli, C. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Palumbo, G. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Chiariello, P. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Marone, G. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Condorelli, M. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Chiariello, M. in: JCI | PubMed | Google Scholar

Department of Medicine, Federico II School of Medicine, Naples, Italy.

Find articles by Triggiani, M. in: JCI | PubMed | Google Scholar

Published June 1, 1994 - More info

Published in Volume 93, Issue 6 on June 1, 1994
J Clin Invest. 1994;93(6):2408–2416. https://doi.org/10.1172/JCI117248.
© 1994 The American Society for Clinical Investigation
Published June 1, 1994 - Version history
View PDF
Abstract

Platelet-activating factor (PAF) can exert profound inflammatory effects at very low concentrations. In plasma, PAF is hydrolyzed to lyso-PAF by acetylhydrolase, an enzyme that circulates bound to LDL. Previous studies suggest that oxygen radicals may act synergistically with PAF to potentiate tissue injury. However, mechanisms underlying this interaction have not been elucidated. In this study we investigated whether oxygen radicals may inactivate PAF acetylhydrolase. PAF acetylhydrolase activity was measured in human plasma and purified LDL before and after exposure to radicals (10-20 nmol/min per ml) generated by xanthine/xanthine oxidase. Oxygen radicals induced > 50% loss of PAF acetylhydrolase activity within 60 s and almost complete inactivation by 10 min. This phenomenon was irreversible and independent of oxidative modification of LDL. Inactivation occurred without changes in the affinity constant of the enzyme (Km was 17.9 microM under control conditions and 15.1 microM after exposure to oxygen radicals). Inactivation was prevented by the scavengers superoxide dismutase or dimethylthiourea or by the iron chelator deferoxamine. Thus, superoxide-mediated, iron-catalyzed formation of hydroxyl radicals can rapidly and irreversibly inactivate PAF acetylhydrolase. Since concomitant production of PAF and oxygen radicals can occur in various forms of tissue injury, inactivation of acetylhydrolase might represent one mechanism by which oxygen radicals may potentiate and prolong the proinflammatory effects of PAF.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

Version history
  • Version 1 (June 1, 1994): No description
Advertisement
Advertisement