The regulation and cellular functions of phosphatidylcholine hydrolysis

Billah, M. Motasim; Anthes, John C.

doi:10.1042/bj2690281

Cited by 840 publications

(446 citation statements)

References 137 publications

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“…Rapid hydrolysis of phosphatidylcholine (PtdCho) mediated by phospholipase D has been documented in various cell types, including neutrophils (24)(25)(26)(27)(28)(29)(30)(31). Hydrolysis of PtdCho by phospholipase D leads to the generation of a potential second messenger, phosphatidic acid (PtdOH) (32)(33)(34).…”

Section: (3-6)mentioning

confidence: 99%

Crystal‐induced neutrophil activation. II. evidence for the activation of a phosphatidylcholine‐specific phospholipase D

Naccache

Bourgoin

Plante

et al. 1993

Arthritis & Rheumatism

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Objective. To investigate the involvement of phospholipase D in the signaling pathways activated by 2 pathologically relevant inflammatory microcrystals, monosodium urate (MSU) and calcium pyrophosphate dihydrate (CPPD).Methods. Human peripheral blood neutrophils were used throughout. Phospholipase D activity was monitored by measuring 3 separate indices: 1) the mass of phosphatidic acid, 2) the levels of alkyl-phosphatidic acid, and 3) the levels of formation, in the presence of ethanol, of phosphatidylethanol. The latter 2 parameters were measured in cells labeled with 1-0-3H-alkyl-2-acetyl-sn-glycero-3-phosphocholine. The cells were stimulated with microcrystals of triclinic morphology.Results. Both MSU and CPPD crystals induced a time-and concentration-dependent accumulation of phosphatidic acid mass and elevation in levels of alkylphosphatidic acid and phosphatidylethanol in prelabeled cells. The activation of phospholipase D by the microcrystals was partially sensitive to colchicine and largely resistant to pertussis toxin. Inhibition of phosphatidic acid formation by wortmannin or ethanol reduced the microcrystal-stimulated production of superoxide anions.Conclusion. These results indicate that microcrystals stimulate phospholipase D in human neutrophils and that at least some of the functional consequences of neutrophil-microcrystal interactions may be dependent on this biochemical pathway.A significant body of evidence indicates that an interaction of monosodium urate (MSU) or of calcium pyrophosphate dihydrate (CPPD) crystals with neutrophils is involved in the etiology of gouty arthritis and of articular chondrocalcinosis, respectively ( 1,2). This conclusion is supported, inter alia, by the presence of microcrystals in the synovial environment including the synovial fluid, and by the ability to reproduce the major symptoms of gout and articular chondrocalcinosis by introduction of these crystals into normal joints (3-6).Microcrystals interact with all of the major synovial cell types, including neutrophils, monocyte/

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Section: (3-6)mentioning

confidence: 99%

Crystal‐induced neutrophil activation. II. evidence for the activation of a phosphatidylcholine‐specific phospholipase D

Naccache

Bourgoin

Plante

et al. 1993

Arthritis & Rheumatism

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“…For example, the in vivo pressor effects of ET are long-lasting, and ET causes a slowly developing and sustained contraction of vascular smooth muscle strips . Phorbol esters also induce sustained activation of PLD in various cell types (Billah and Anthes, 1990;Pai et al, 1991) and, similar to ET, they induce sustained contraction of vascular smooth muscle (Rasmussen et al, 1984). It is possible that the mitogenic response elicited by ET and phorbol esters in R6-PKC3 cells and the persistent nature of vascular smooth muscle contraction induced by these agents can be attributed to the prolonged activation of PLD.…”

Section: Discussionmentioning

confidence: 99%

“…PEt formation in the presence of ethanol is an unambiguous marker of PLD activation (Pai et al, 1 988a,b;Billah and Anthes, 1990;Kanfer, 1980). Induction of [3H]PEt formation by ET-1 was dose-dependent ( Figure 2).…”

Section: Introductionmentioning

confidence: 94%

“…Three genes encoding homologous endothelin peptides-ET-1, ET-2, and ' Abbreviations used: DAG, 1,2-sn-diacylglycerol; DMEM, Dulbecco's modified Eagle's medium; DMSO, dimethyl sulfoxide; ET, endothelin; PA, phosphatidic acid; PC, phosphatidylcholine; PEt, phosphatidylethanol; PLD, phospholipase D; PMA, phorbol-1 2-myristate-1 3-acetate; PKC, protein kinase C; R6-C1, control Rat-6 fibroblasts; R6-PKC3, PKC overexpressing cells; TCA, trichloroacetic acid. ©) 1991 by The American Society for Cell Biology Recent evidence indicates that many receptors coupled to inositol phospholipid hydrolysis are also coupled (directly or indirectly) to a distinct phospholipase, phospholipase D (PLD) (Billah and Anthes, 1990). PLD catalyzes hydrolysis of the terminal diester bond of phosphatidylcholine (PC) (and possibly other glycerophosphatides) with the formation of phosphatidic acid (PA) and choline.…”

Section: Introductionmentioning

confidence: 99%

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Endothelin-1 activates phospholipase D and thymidine incorporation in fibroblasts overexpressing protein kinase C beta 1.

Pai¹,

Dobek²,

Bishop³

1991

Cell Regul

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[H]DAG from PC by the sequential action of PLD and PA phosphohydrolase. Phorbol esters are known to stimulate thymidine incorporation and PLD activity to a greater extent in PKC overexpressing cells than in control cells. ET-1 also stimulates thymidine incorporation to a greater extent in the PKC overexpressing cells. The effect of ET-1 on thymidine incorporation into DNA in the overexpressing cells was also dose-dependent with a half-maximal effect at 0.3 x 10-9 M. Enhanced PLD activity induced by ET-1 in the overexpressing cells may contribute to the mitogenic response, especially in light of a possible role of the PLD product, PA, in regulation of cell growth.

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“…DAG stimulates one or more members of a family of kinases known collectively as protein kinase C, which are established as key enzymes in mitogenesis. 9,10 Activated protein kinase C then stimulates another phospholipase, phospholipase D (PLD), 11,12 resulting in the breakdown of phosphatidylcholine and/or phosphatidylethanolamine with the subsequent production of phosphatidic acid (PA) and the release of choline and/or ethanolamine. In fibroblast cell lines, PLD activation has been implicated in PDGF-stimulated proliferation 13 and exogenous PA has been shown to induce DNA synthesis.…”

mentioning

confidence: 99%

The role of phosphatidic acid in platelet-derived growth factor-induced proliferation of rat hepatic stellate cells

et al. 2000

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Platelet-derived growth factor (PDGF) is the most potent mitogen for hepatic stellate cells (HSCs) in vitro. The aim of this study was to investigate the role of the lipid-derived second messenger phosphatidic acid (PA) in mediating this effect and, in particular, to determine its interaction with the extracellular signal-regulated kinase (ERK) cascade. HSCs were isolated from rat livers. PA production was determined by lipid extraction and thin-layer chromatography (TLC) after prelabeling cells with [ 3 H]myristate. ERK activity was measured by an in vitro kinase assay after immunoprecipitation. Mitogenic concentrations of PDGF, but not those of the relatively less potent mitogen, transforming growth factor ␣ (TGF-␣), stimulated the sustained production of PA from HSCs. Exogenous PA stimulated HSC proliferation and a sustained increase in ERK activity, and proliferation was completely blocked by the inhibition of ERK activation with PD98059. The stimulation of ERK by PDGF was of a similar magnitude but more sustained than that caused by TGF-␣. These results suggest that the potent mitogenic effect of PDGF in HSCs may be caused, in part, by the generation of PA and subsequently by a more sustained activation of ERK than occurs with less potent mitogens that do not induce the production of this lipid second messenger. (HEPATOLOGY 2000;31:95-100.)Hepatic stellate cells (HSCs) are regarded as the principal cell type responsible for the development and progression of liver fibrosis. 1 After liver injury, they transform from quiescent cells into myofibroblast-like cells that proliferate in response to platelet-derived growth factor (PDGF), epidermal growth factor, transforming growth factor ␣ (TGF-␣), and basic fibroblast growth factor. As the most potent mitogen, studies aimed at understanding the signaling mechanisms involved in HSC mitogenesis have focused largely on PDGF. The PDGF receptor consists of 2 subunits with intrinsic tyrosine kinase activity. After ligand binding, the subunits autophosphorylate several tyrosine residues, 2 which then act as binding sites for molecules containing src homology 2 domains. 3 These include the adaptor protein Grb2, which recruits the Ras-activating protein, Sos, and triggers a kinase cascade that results in the sequential activation of Raf-1, mitogen-activated protein kinase kinase and the extracellular signal-regulated kinases, ERK1 and ERK2. 4 Recently, studies in HSCs 5 and many other cell types 6 have established an important role for this mitogen-activated protein kinase cascade in the proliferative response.A second protein recruited to the autophosphorylated PDGF receptor by virtue of its src homology 2 domain is phospholipase C ␥ (PLC-␥). 7,8 Once at the plasma membrane, PLC-␥ initiates a distinct signaling cascade beginning with the hydrolysis of phosphatidylinositol 4,5-bisphosphate to inositol 1,4,5-trisphosphate and diacylglycerol (DAG). DAG stimulates one or more members of a family of kinases known collectively as protein kinase C, which are established as key ...

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The regulation and cellular functions of phosphatidylcholine hydrolysis

Cited by 840 publications

References 137 publications

Crystal‐induced neutrophil activation. II. evidence for the activation of a phosphatidylcholine‐specific phospholipase D

Crystal‐induced neutrophil activation. II. evidence for the activation of a phosphatidylcholine‐specific phospholipase D

Endothelin-1 activates phospholipase D and thymidine incorporation in fibroblasts overexpressing protein kinase C beta 1.

The role of phosphatidic acid in platelet-derived growth factor-induced proliferation of rat hepatic stellate cells

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