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

Marathe, Gopal Kedihithlu and Chaithra, Vyala Hanumanthareddy and Ke, Liang-Yin and Chen, Chu-Huang (2020) Effect of acyl and alkyl analogs of platelet-activating factor on inflammatory signaling. Prostaglandins & Other Lipid Mediators, 151. ISSN 2212-196X

Full text not available from this repository. (Request a copy)
Official URL: https://www.sciencedirect.com/science/article/abs/...


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 bio-synthesis, 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, PAFAH, 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.

Item Type: Article
Uncontrolled Keywords: PAF; PAF Analog; PAF-receptor; PAF-acetylhydrolases; PAF-R antagonist
Subjects: C Chemical Science > Biochemistry
Divisions: Department of > Biochemistry
Depositing User: Mr Umendra uom
Date Deposited: 01 Apr 2021 06:24
Last Modified: 01 Apr 2021 06:24
URI: http://eprints.uni-mysore.ac.in/id/eprint/15465

Actions (login required)

View Item View Item