To hydrolyze or not to hydrolyze: The dilemma of platelet-activating factor acetylhydrolase

Marathe, G. K. and Pandit, C. and Lakshmikanth, C. L. and Chaithra, V. H. and Jacob, S. P. and D'Souza, C. J. M. (2014) To hydrolyze or not to hydrolyze: The dilemma of platelet-activating factor acetylhydrolase. Journal of Lipid Research, 55 (9). pp. 1847-1854. ISSN 0022-2275

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Abstract

Mounting ambiguity persists around the functional role of the plasma form of platelet-activating factor acetylhydrolase (PAF-AH). Because PAF-AH hydrolyzes PAF and related oxidized phospholipids, it is widely accepted as an anti-inflammatory enzyme. On the other hand, its actions can also generate lysophosphatidylcholine (lysoPC), a component of bioactive atherogenic oxidized LDL, thus allowing the enzyme to have proinflammatory capabilities. Presence of a canonical lysoPC receptor has been seriously questioned for a multitude of reasons. Animal models of inflammation show that elevating PAF-AH levels is beneficial and not deleterious and overexpression of PAF receptor (PAF-R) also augments inflammatory responses. Further, many Asian populations have a catalytically inert PAF-AH that appears to be a severity factor in a range of inflammatory disorders. Correlation found with elevated levels of PAF-AH and CVDs has led to the design of a specific PAF-AH inhibitor, darapladib. However, in a recently concluded phase III STABILITY clinical trial, use of darapladib did not yield promising results. Presence of structurally related multiple ligands for PAF-R with varied potency, existence of multi-molecular forms of PAF-AH, broad substrate specificity of the enzyme and continuous PAF production by the so called bi-cycle of PAF makes PAF more enigmatic. This review seeks to address the above concerns.

Item Type:	Article
Uncontrolled Keywords:	human, animal, Animals, Humans, immunology, physiology, risk factor, Risk Factors, enzymology, hydrolysis, Hydrolysis, Inflammation Mediators, 1-Alkyl-2-acetylglycerophosphocholine Esterase, autacoid, 1 alkyl 2 acetylglycerophosphocholine esterase, atherosclerosis, Atherosclerosis, Platelet Activating Factor, thrombocyte activating factor
Subjects:	C Chemical Science > Biochemistry
Divisions:	Department of > Biochemistry
Depositing User:	Arshiya Kousar Library Assistant
Date Deposited:	28 Jun 2019 10:29
Last Modified:	28 Jun 2019 10:31
URI:	http://eprints.uni-mysore.ac.in/id/eprint/3983

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