To hydrolyse or not to hydrolyse: the dilemma of platelet activating factor acetylhydrolase (PAF-AH)

Marathe, Gopal K. and Pandit, Chaitanya and Lakshmikanth, C. L. and Chaithra, V. H. and Jacob, Shancy Petsel and D'Souza, Cletus J. M. (2014) To hydrolyse or not to hydrolyse: the dilemma of platelet activating factor acetylhydrolase (PAF-AH). Journal of Lipid Research . pp. 1-28.

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Mounting ambiguity persists around the functional role of the plasma form of platelet-activating factor acetylhydrolase (PAF-AH). Since PAF-AH hydrolyses 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 pro-inflammatory 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-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
Additional Information: Unmapped bibliographic data: JO - Journal of Lipid Research [Field not mapped to EPrints]
Subjects: Agriculture Biological Sciences > Biochemistry
University of Mysore > PG Campuses > Manasagangotri, Mysore > Agriculture Biological Sciences > Biochemistry
Divisions: PG Campuses > Manasagangotri, Mysore > Biochemistry
Depositing User: Praveen Kumari B.L
Date Deposited: 04 Jun 2014 06:16
Last Modified: 20 Oct 2015 10:15

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