Platelet-activating factor acetylhydrolases in health and disease

Tjoelker, Larry W.; Stafforini, Diana M.

doi:10.1016/s1388-1981(00)00114-1

Cited by 150 publications

(118 citation statements)

References 169 publications

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“…Our results are consistent with a previous study showing strict substrate specificity of the enzyme for an acetate at the sn-2 position of a phospholipid (18). It has been proposed that PAF in the brain plays an important role as a messenger in excitatory neurotransmitter release, neuronal plasticity, memory formation, and long-term potentiation (reviewed in ref 44). It was also postulated that 1-Oalkyl-2-acetyl-phospholipids other than PAF such as alk-1-enyl-acetyl-glycerophosphoethanolamine (2-acetylplasmalogen) may be physiological substrates for PAF-AH(Ib) (45).…”

Section: Discussionsupporting

confidence: 93%

Platelet-Activating Factor Acetylhydrolases: Broad Substrate Specificity and Lipoprotein Binding Does Not Modulate the Catalytic Properties of the Plasma Enzyme

et al. 2001

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Platelet-activating factor acetylhydrolases (PAF-AHs) are a group of enzymes that hydrolyze the sn-2 acetyl ester of PAF (phospholipase A 2 activity) but not phospholipids with two long fatty acyl groups. Our previous studies showed that membrane-bound human plasma PAF-AH (pPAF-AH) accesses its substrate only from the aqueous phase, which raises the possibility that this enzyme can hydrolyze a variety of lipid esters that are partially soluble in the aqueous phase. Here we show that pPAF-AH has broad substrate specificity in that it hydrolyzes short-chain diacylglycerols, triacylglycerols, and acetylated alkanols, and displays phospholipase A 1 activity. On the basis of all of the substrate specificity results, it appears that the minimal structural requirement for a good pPAF-AH substrate is the portion of a glyceride derivative that includes an sn-2 ester and a reasonably hydrophobic chain in the position occupied by the sn-1 chain. In vivo, pPAF-AH is bound to high and low density lipoproteins, and we show that the apparent maximal velocity for this enzyme is not influenced by lipoprotein binding and that the enzyme hydrolyzes tributyroylglycerol as well as the recombinant pPAF-AH does. Broad substrate specificity is also observed for the structurally homologous PAF-AH which occurs intracellularly [PAF-AH(II)] as well as for the PAF-AH from the lower eukaryote Physarum polycephalum although pPAF-AH and PAF-AH(II) tolerate the removal of the sn-3 headgroup better than the PAF-AH from P. polycephalum does. In contrast, the intracellular PAF-AH found in mammalian brain [PAF-AH(Ib) R1/R1 and R2/R2 homodimers] is more selectively operative on compounds with a short acetyl chain although this enzyme also displays significant phospholipase A 1 activity.

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Section: Discussionsupporting

confidence: 93%

Platelet-Activating Factor Acetylhydrolases: Broad Substrate Specificity and Lipoprotein Binding Does Not Modulate the Catalytic Properties of the Plasma Enzyme

et al. 2001

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“…13 Due to their highly sensitive nature, platelets can be activated by many different molecules resulting in morphological changes followed by release or uptake of specific proteins. 14,15,16,17,18 Thereby platelets can release certain proteins where they are needed, such as fibrinogen at the location of a wound 19 or growth proteins such as VEGF at the location of rapid cell division. 20 Details of how proteins are stored in platelets thus carry a wealth of information regarding the status of our bodies and can potentially provide diagnostic indicators of different states and diseases, including cancer.…”

Section: Multic and Itsmentioning

confidence: 99%

Multicolor Fluorescence Nanoscopy by Photobleaching: Concept, Verification, and Its Application To Resolve Selective Storage of Proteins in Platelets

Rönnlund

Perols

et al. 2014

ACS Nano

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Fluorescence nanoscopy provides means to discern the finer details of protein localization and interaction in cells by offering an order of magnitude higher resolution than conventional optical imaging techniques. However, these super resolution techniques put higher demands on the optical system and the fluorescent probes, making multicolor fluorescence nanoscopy a challenging task. Here we present a new and simple procedure, which exploits the photostability and excitation spectra of dyes to increase the number of simultaneous recordable targets in STED nanoscopy. We use this procedure to demonstrate four-color STED imaging of platelets with e40 nm resolution and low crosstalk. Platelets can selectively store, sequester, and release a multitude of different proteins, in a manner specific for different physiological and disease states. By applying multicolor nanoscopy to study platelets, we can achieve spatial mapping of the protein organization with a high resolution for multiple proteins at the same time and in the same cell. This provides a means to identify specific platelet activation states for diagnostic purposes and to understand the underlying protein storage and release mechanisms. We studied the organization of the pro-and antiangiogenic proteins VEGF and PF-4, together with fibrinogen and filamentous actin, and found distinct features in their respective protein localization. Further, colocalization analysis revealed only minor overlap between the proteins VEGF and PF-4 indicating that they have separate storage and release mechanisms, corresponding well with their opposite roles as pro-and antiangiogenic proteins, respectively.

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“…Phospholipids with a pro-inflammatory activity may be generated through oxidative fragmentation of the phosphatidylcholine fatty acid, which are known as PAF-like phospholipids. The biological activity of PAF and PAF-like phospholipids is attenuated by phospholipase A2 enzymes (PLA2) 11 .…”

Section: Introductionmentioning

confidence: 99%

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

Castro¹,

Neto²,

Gomes³

2007

Arq. Bras. Cardiol.

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SummaryObjective: To evaluate platelet-activating factor acetylhydrolase (PAF-AH) activity and its relationship with clinical and demographic variables, metabolic control, apolipoprotein A and B levels and the susceptibility of low-density lipoprotein (LDL) to in vitro oxidation in patients with type 1 diabetes mellitus (DM 1).Methods: Forty two patients with DM 1 (27 females) and 48 control subjects (16 females) matched for gender, age and body mass index (BMI) were evaluated. The following tests were performed: fast plasma glucose (FG) and postprandial plasma glucose (PPG), lipid profile, uric acid (UA), glycosylated hemoglobin (HbA1c), and low-density lipoprotein (LDL) oxidation rate using colorimetric assay. The PAF-AH activity was analyzed using colorimetric assay (Cayman Chemical).Results: The analysis of PAF-AH activity showed a higher enzyme activity in patients with DM 1 than in control subjects (0.0150 + 0.0051 vs. 0.0116 + 0.0041; p < 0.001). In patients with DM 1, a direct correlation between PAF-AH activity and age and LDL, and an inverse correlation between PAF-AH and HbA1c and high-density lipoprotein (HDL) were found.Conclusion: In the sample studied, PAF-AH showed a higher activity in patients with DM 1, a factor that may be related to the higher risk of developing cardiovascular diseases observed in these patients. Further studies are necessary to evaluate the real participation of this enzyme in the risk of development of atherosclerotic diseases in patients with DM 1.

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Platelet-activating factor acetylhydrolases in health and disease

Cited by 150 publications

References 169 publications

Platelet-Activating Factor Acetylhydrolases: Broad Substrate Specificity and Lipoprotein Binding Does Not Modulate the Catalytic Properties of the Plasma Enzyme

Platelet-Activating Factor Acetylhydrolases: Broad Substrate Specificity and Lipoprotein Binding Does Not Modulate the Catalytic Properties of the Plasma Enzyme

Multicolor Fluorescence Nanoscopy by Photobleaching: Concept, Verification, and Its Application To Resolve Selective Storage of Proteins in Platelets

Atividade da enzima acetil-hidrolase do fator ativador de plaquetas (PAF-AH) em pacientes com diabete melito tipo 1

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