Effect of acyl and alkyl analogs of platelet-activating factor on inflammatory signaling.

Autor: Marathe GK; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India; Department of Studies in Molecular Biology, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India. Electronic address: marathe1962@gmail.com., Chaithra VH; Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysuru, 570006, Karnataka, India. Electronic address: chaitravh0809@gmail.com., Ke LY; College of Health Sciences, Kaohsiung Medical University, Vascular and Medicinal Research, Kaohsiung, 80708, Taiwan. Electronic address: kly@gap.kmu.edu.tw., Chen CH; Vascular and Medicinal Research, Texas Heart Institute, Houston, Texas 77030, USA. Electronic address: cchen@texasheart.org.
Jazyk: angličtina
Zdroj: Prostaglandins & other lipid mediators [Prostaglandins Other Lipid Mediat] 2020 Dec; Vol. 151, pp. 106478. Date of Electronic Publication: 2020 Jul 22.
DOI: 10.1016/j.prostaglandins.2020.106478
Abstrakt: Platelet-activating factor (PAF), a bioactive ether phospholipid with significant pro-inflammatory properties, was identified almost half a century ago. Despite extensive study of this autocoid, therapeutic strategies for targeting its signaling components have not been successful, including the recent clinical trials with darapladib, a drug that targets plasma PAF-acetylhydrolase (PAF-AH). We recently provided experimental evidence that the previously unrecognized acyl analog of PAF, which is concomitantly produced along with PAF during biosynthesis, dampens PAF signaling by acting both as a sacrificial substrate for PAF-AH and probably as an endogenous PAF-receptor antagonist/partial agonist. If this is the scenario in vivo, PAF-AH needs to catalyze the selective hydrolysis of alkyl-PAF and not acyl-PAF. Accordingly, different approaches are needed for treating inflammatory diseases in which PAF signaling is implicated. The interplay between acyl-PAF, alkyl-PAF, PAF-AH, and PAF-R is complex, and the outcome of this interplay has not been previously appreciated. In this review, we discuss this interaction based on our recent findings. It is very likely that the relative abundance of acyl and alkyl-PAF and their interactions with PAF-R in the presence of their hydrolyzing enzyme PAF-AH may exert a modulatory effect on PAF signaling during inflammation.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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