Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma form of platelet-activating factor (PAF) acetylhydrolase (PAF-AH), also known as lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) 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.
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PMID:Identification of a domain that mediates association of platelet-activating factor acetylhydrolase with high density lipoprotein. 1843 4

The plasma form of PAF-AH [PAF (platelet-activating factor) acetylhydrolase; also known as LpPLA(2) (lipopoprotein-associated phospholipase A(2)), PLA(2)G7] catalyses the release of sn-2 fatty acyl residues from PAF, oxidatively fragmented phospholipids, and esterified isoprostanes. The plasma levels of this enzyme vary widely among mammalian species, including mice and humans, but the mechanisms that account for these differences are largely unknown. We investigated the basis for these variations using molecular and biochemical approaches. We identified an N-terminal domain that played key roles in the determination of steady-state expression levels. The mouse N-terminal domain robustly enhanced protein expression levels, possibly owing to its ability to adopt a globular conformation that is absent in the human protein. We investigated the mechanism(s) whereby the N-terminal stretch modulated PAF-AH levels and found that differential expression was not due to variations in the efficiency of transcription, translation, or mRNA stability. Studies designed to evaluate the ability of precursor forms of PAF-AH to mature to fully active proteins indicated that the N-terminal end of human and mouse PAF-AH played important and opposite roles in this process. These domains also modulated the levels of expression of an unrelated polypeptide by affecting the stability of precursor forms of the protein. These studies provide insights that contribute to our understanding of the molecular features and mechanisms that contribute to differential expression of plasma PAF-AH in mammals.
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PMID:Novel mechanism for regulation of plasma platelet-activating factor acetylhydrolase expression in mammalian cells. 2033 34