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

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 hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase. Journal of Lipid Research, 55 (9). pp. 1847-1854.

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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
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: 02 Mar 2015 09:24
Last Modified: 02 Mar 2015 09:24

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