The role of lipoproteins in the degradation of platelet-activating factor

Ostermann, G; Kertscher, H.‐P.; Winkler, L; Schlag, B; Rühling, K.; Till, U

doi:10.1016/0049-3848(86)90005-8

Cited by 28 publications

(14 citation statements)

References 15 publications

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“…others (13,59) performed functional studies under conditions that prevail in vivo, we found that the environment in which PAF-AH exists influenced its catalytic activity. These findings were confirmed using a variety of independent approaches, and they established that PAF-AH is more active against subsaturating concentrations of PAF if it is localized in LDL versus HDL particles.…”

Section: Discussionmentioning

confidence: 95%

Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein

Gardner

Reichert

Topham

et al. 2008

Journal of Biological Chemistry

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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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Section: Discussionmentioning

confidence: 95%

Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein

Gardner

Reichert

Topham

et al. 2008

Journal of Biological Chemistry

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“…These investigators also reported that the activity of this enzyme was associated with a lipoprotein (20). Ostermann et al (22) reported that the PAF acetylhydrolase activity was associated with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions and was 10-and 100-fold higher than that found in high density lipoprotein (HDL) and serum, respectively. Stafforini et al (23,24) have purified PAF acetylhydrolase from human plasma.…”

mentioning

confidence: 84%

“…It has been reported (20,22) that the activity of this enzyme was closely associated with the LDL fraction of human plasma. Stafforini et al (23) have purified to near homogeneity the plasma enzyme from a human LDL fraction and have also suggested that the biologically active acetylhydrolase was associated with the LDL fraction, although significant activity was also present in the HDL fraction.…”

Section: Discussionmentioning

confidence: 99%

Platelet-activating factor acetylhydrolase activity in maternal, fetal, and newborn rabbit plasma during pregnancy and lactation.

Maki

Hoffman

Johnston

1988

Proc. Natl. Acad. Sci. U.S.A.

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The inactivation of the biologically active ether-containing glycerophospholipid platelet-activating factor (PAF) is catalyzed by the enzyme PAF acetylhydrolase (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase, EC 3.1.1.48). The specific activity of acetylhydrolase has been assayed in maternal rabbit plasma prior to and throughout pregnancy and after parturition. The specific activity of acetylhydrolase was 131 + 8 nmol-min -'ml'-of plasma (mean ± SEM) in the nonpregnant rabbit. Similar specific activities were found throughout the first half of pregnancy; however, on day 15 the acetylhydrolase activity began to decrease and reached a minimum around day 27. Within 24-48 hr following delivery, the specific activity of the enzyme increased to the levels found in the nonpregnant animals. The specific activity of acetylhydrolase in fetuses (gestational ages of 21-30 days) and neonates increased from 22 nmol min'-1 ml-1 of plasma (21-day-old) to 328 nmolinin ml' of plasma (35-day-old rabbits). The decrease in enzymatic activity of the pregnant rabbit plasma cannot be accounted for by the presence of an inhibitor as determined by plasma-mixing experiments with nonpregnant and pregnant (27-day) plasma. The properties of this enzyme in the rabbit were consistent with those reported by others, i.e., substrate specificity, inactivation by heat and various inhibitors, and Ca2" inde-

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“…Ostermann et al (8) used two different assays to examine the ability ofisolated lipoproteins to catalyze the hydrolysis ofPAF. They measured the release of radiolabeled acetate from PAF, an assay similar to our optimized assay except that their concentration of substrate (11 uM) was just at the Km (9) instead of severalfold higher.…”

Section: Discussionmentioning

confidence: 99%

Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.

Stafforini

Carter

Zimmerman

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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Platelet-activating factor (PAF) has been implicated as a mediator of inflammation, allergy, shock, and thrombosis. A specific degradative enzyme, PAF acetyihydrolase (EC 3.1.1.47), is found in plasma and could regulate the concentration of PAF in blood. In plasma, 70% of the PAF acetylhydrolase is found with low density lipoprotein (LDL), and the remainder is in high density lipoprotein (HDL). In previous studies we found that with subsaturating concentrations of PAF the activity in LDL seemed to be the relevant one; e.g., depletion of LDL slowed degradation of PAF, while removal of HDL accelerated the degradation slightly. We have pursued this observation by using plasma from humans with lipoprotein mutations. In abetalipoproteinemia, all of the PAF acetylhydrolase activity was in HDL, whereas in Tangier disease all of the activity was in LDL. In both conditions the total activity measured in an optimized assay was normal or increased. However, when we measured the t1/2 of PAF in plasma, we found that it was prolonged in subjects with abetalipoproteinemia compared to normal controls. Conversely, the t1/2 in Tangier plasma was shortened. We next demonstrated that the PAF acetylhydrolase in HDL was recognized by an antibody to the enzyme purified from LDL, establishing that the enzyme in the two particles is the same protein. Finally, we inactivated the PAF acetylhydrolase in isolated lipoprotein particles and then reconstituted them with enzyme from the opposite particle. The reconstituted particles were used to measure the t1/2 of PAF, and we again found that the LDL particle was more efficient. We conclude that the lipoprotein environment of the PAF acetylhydrolase markedly influences its catalytic behavior. This may be important in pathophysiology and will complicate attempts to assess the role of this enzyme in such circumstances.

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The role of lipoproteins in the degradation of platelet-activating factor

Cited by 28 publications

References 15 publications

Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein

Identification of a Domain That Mediates Association of Platelet-activating Factor Acetylhydrolase with High Density Lipoprotein

Platelet-activating factor acetylhydrolase activity in maternal, fetal, and newborn rabbit plasma during pregnancy and lactation.

Lipoproteins alter the catalytic behavior of the platelet-activating factor acetylhydrolase in human plasma.

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