Subcellular localization of phospholipids and enzymes involved in PAF‐acether metabolism

Record, Michel; Ribbes, Gérard; Tercé, François; Chap, Hugues

doi:10.1002/jcb.240400311

Cited by 27 publications

(8 citation statements)

References 43 publications

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“…We employed microsomes from unstimulated cells as our acetyltransferase source and evaluated the effect of various recombinant, constitutively activated MAP kinases on acetyltransferase activity. It has been recognized for some time that the acetyltransferase is localized in an internal membrane source (32,33), and although the compartment has not been unequivocally determined, it has been suggested that it resides in either the tertiary granule or endoplasmic reticulum membranes (34). Regardless of the exact source, microsomal fractions were found to contain the highest specific activity of acetyltransferase activity.…”

Section: Activation Of Map Kinase(s) and Acetyltransferase By Tnf-␣ mentioning

confidence: 99%

Acetyl-CoA:1-O-Alkyl-2-lyso-sn-glycero-3-phosphocholine Acetyltransferase Is Directly Activated by p38 Kinase

Nixon¹,

O’Flaherty²,

Salyer³

et al. 1999

Journal of Biological Chemistry

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Acetyl-CoA:1-O-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase, along with phospholipase A 2 , is a key regulator of platelet-activating factor biosynthesis via the remodeling pathway. We have now obtained evidence in human neutrophils indicating that this enzyme is regulated by a specific member of the mitogenactivated protein kinases, namely the p38 kinase. We earlier demonstrated that tumor necrosis factor-␣ (TNF-␣) as well as N-formyl-methionyl-leucyl-phenylalanine treatment leads to increased phosphorylation and activation of p38 kinase in human neutrophils. Strikingly, in the present study these stimuli increased the catalytic activity of acetyltransferase up to 3-fold, whereas 4-phorbol 12-myristate 13-acetate, which activates the extracellular-regulated kinases (ERKs) but not p38 kinase, had no effect. Furthermore, a selective inhibitor of p38 kinase, SB 203580, was able to abolish the TNF-␣-and N-formyl-methionyl-leucyl-phenylalanineinduced activation of acetyltransferase. The same effect was not observed in the presence of an inhibitor that blocked ERK activation (PD 98059). Complementing the findings in intact cells, we have shown that recombinant, activated p38 kinase added to microsomes in the presence of Mg 2؉ and ATP increased acetyltransferase activity to the same degree as in microsomes obtained from TNF-␣-stimulated cells. No activation of acetyltransferase occurred upon treatment of microsomes with either recombinant, activated ERK-1 or ERK-2. Finally, the increases in acetyltransferase activity induced by TNF-␣ could be ablated by treating the microsomes with alkaline phosphatase. Thus acetyltransferase appears to be a downstream target for p38 kinase but not ERKs. These data from whole cells as well as cell-free systems fit a model wherein stimulus-induced acetyltransferase activation is mediated by a phosphorylation event catalyzed directly by p38 kinase.

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Section: Activation Of Map Kinase(s) and Acetyltransferase By Tnf-␣ mentioning

confidence: 99%

Acetyl-CoA:1-O-Alkyl-2-lyso-sn-glycero-3-phosphocholine Acetyltransferase Is Directly Activated by p38 Kinase

Nixon¹,

O’Flaherty²,

Salyer³

et al. 1999

Journal of Biological Chemistry

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“…The process may be regulated at the level of either lipid synthesis or at the dedicated lysoglycerophosphate acetyltransferase and cholinephosphotransferase [25]. In contrast, the stimulated PAF synthesis via the remodelling pathway [26] is induced by cellspecific stimuli such as the inflammatory mediator thrombin [23]. It can be triggered non-specifically by Ca# + ionophores.…”

Section: Discussion Paf Synthesis and Transportmentioning

confidence: 99%

“…It involves a phospholipase A # -catalysed release of arachidonate from the sn-2 position of an alkyl-PC, yielding the PAF-precursor lyso-PAF and the eicosanoid precursor arachidonic acid. Lyso-PAF is converted into PAF by the esterification with acetate, which is catalysed by a specific acetyl-CoA : lyso-PAF acetyltransferase [26].…”

Section: Introductionmentioning

confidence: 99%

Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor

2001

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The human multidrug-resistance (MDR1) P-glycoprotein (Pgp) is an ATP-binding-cassette transporter (ABCB1) that is ubiquitously expressed. Often its concentration is high in the plasma membrane of cancer cells, where it causes multidrug resistance by pumping lipophilic drugs out of the cell. In addition, MDR1 Pgp can transport analogues of membrane lipids with shortened acyl chains across the plasma membrane. We studied a role for MDR1 Pgp in transport to the cell surface of the signal-transduction molecule platelet-activating factor (PAF). PAF is the natural short-chain phospholipid 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine. [(14)C]PAF synthesized intracellularly from exogenous alkylacetylglycerol and [(14)C]choline became accessible to albumin in the extracellular medium of pig kidney epithelial LLC-PK1 cells in the absence of vesicular transport. Its translocation across the apical membrane was greatly stimulated by the expression of MDR1 Pgp, and inhibited by the MDR1 inhibitors PSC833 and cyclosporin A. Basolateral translocation was not stimulated by expression of the basolateral drug transporter MRP1 (ABCC1). It was insensitive to the MRP1 inhibitor indomethacin and to depletion of GSH which is required for MRP1 activity. While efficient transport of PAF across the apical plasma membrane may be physiologically relevant in MDR1-expressing epithelia, PAF secretion in multidrug-resistant tumours may stimulate angiogenesis and thereby tumour growth.

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“…Upon transfer of 1-0-alkyl-2-acyl-GPC from the endoplasmic reticulum to the plasma membrane, the sn-2 position could be removed by hydrolysis to produce lysoPAF. The most efficient pathway for PAF synthesis to occur would be through similar topographical locations for the acetyltransferase and the enzyme responsible for the hydrolytic activity producing lysoPAF from l-O-alkyl-2-acyl-GPC (Record et al 1989). It has been widely accepted that the enzyme responsible for this activity is a phospholipase-A2 (PLA 2 ; EC 3.1.1.4) (Waish et al 1981;Swendsen et al 1983;Pinckard et al 1988;Bauldry et al 1991).…”

Section: Transfer Proteinsmentioning

confidence: 99%

Lipid Mediator Mechanisms in Fish

Samples

Pool

Pritchard

et al. 1997

The Progressive Fish-Culturist

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Salmonids synthesize platelet‐activating factor (PAF: 1‐O‐alkyl‐2‐acetyl‐sn‐glycero‐3‐phosphocholine), and much of the interest in the potential use of lipids to mediate physiological events in fish metabolism is focused on this compound. In sharp contrast to mammalian cells, salmonid cells acylate lysoPAF with a high degree of specificity for omega‐3 fatty acids. Polyunsaturated fatty acids in the lipids in tissues of rainbow trout Oncorhynchus mykiss are compartmentalized differently than in mammalian tissues. On extracellular challenge by PAF, trout leukocytes exhibit both chemotaxis and respiratory burst responses. During the metabolism of PAF in rainbow trout leukocytes, acylation of lysoPAF appears highly selective for docosahexaenoic acid (C22:6 n‐3) and eicosapentaenoic acid (C20:5 n‐3) and is localized in the endoplasmic reticulum. The acyl moiety in the sn‐2 position of the acylation product 1‐O‐alkyl‐2‐acyl‐glycero‐3‐phosphocholine may be removed by hydrolysis to produce lysoPAF in the endoplasmic reticulum, or the acylation product may be transported to the plasma membrane where lysoPAF may be generated. LysoPAF is acetylated at the plasma membrane by an acetyltransferase to produce PAR This PAF is degraded by a cytosolic acetylhydrolase to produce lysoPAF, the substrate for the transacylase. Thus, rainbow trout offer an opportunity to investigate omega‐3 fatty acids as lipid mediators in a system less complex than mammalian systems. The results of such studies are certain to affect future practices in aquaculture as attempts to increase output intensify and stress to cultural animals becomes an inherent problem.

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Subcellular localization of phospholipids and enzymes involved in PAF‐acether metabolism

Cited by 27 publications

References 43 publications

Acetyl-CoA:1-O-Alkyl-2-lyso-sn-glycero-3-phosphocholine Acetyltransferase Is Directly Activated by p38 Kinase

Acetyl-CoA:1-O-Alkyl-2-lyso-sn-glycero-3-phosphocholine Acetyltransferase Is Directly Activated by p38 Kinase

Multidrug-resistance P-glycoprotein (MDR1) secretes platelet-activating factor

Lipid Mediator Mechanisms in Fish

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