7 research outputs found
Regulating inflammation through the anti-inflammatory enzyme platelet-activating factor-acetylhydrolase
Platelet-activating factor (PAF) is one of the most potent lipid mediators involved in inflammatory events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity. Deacetylation induces the formation of the inactive metabolite lyso-PAF. This deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH), a calcium independent phospholipase A2 that also degrades a family of PAF-like oxidized phospholipids with short sn-2 residues. Biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Many observations indicate that plasma PAF AH terminates signals by PAF and oxidized PAF-like lipids and thereby regulates inflammatory responses. In this review, we will focus on the potential of PAF-AH as a modulator of diseases of dysregulated inflammation
Intravascular adenovirus-mediated lipoprotein-associated phospholipase A2 gene transfer reduces neointima formation in balloon-denuded rabbit aorta
Lipoprotein-Associated Phospholipase A2 Predicts Progression of Cardiac Allograft Vasculopathy and Increased Risk of Cardiovascular Events in Heart Transplant Patients
Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein*S⃞
The plasma form of platelet-activating factor (PAF) acetylhydrolase
(PAF-AH), also known as lipoprotein-associated phospholipase A2
(Lp-PLA2) inactivates potent lipid messengers such as PAF and
modified phospholipids generated in settings of oxidant stress. In humans,
PAF-AH circulates in blood in fully active form and associates with high and
low density lipoproteins (HDL and LDL). Several studies suggest that the
location of PAF-AH affects both the catalytic efficiency and the function of
the enzyme in vivo. The distribution of PAF-AH among lipoproteins
varies widely among mammals. Here, we report that mouse and human PAF-AHs
associate with human HDL particles of different density. We made use of this
observation in the development of a binding assay to identify domains required
for association of human PAF-AH with human HDL. Sequence comparisons among
species combined with domain-swapping and site-directed mutagenesis studies
led us to the identification of C-terminal residues necessary for the
association of human PAF-AH with human HDL. Interestingly, the region
identified is not conserved among PAF-AHs, suggesting that PAF-AH interacts
with HDL particles in a manner that is unique to each species. These findings
contribute to our understanding of the mechanisms responsible for association
of human PAF-AH with HDL and may facilitate future studies aimed at precisely
determining the function of PAF-AH in each lipoprotein particle