12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates

Tettenborn, Connie S.; Mueller, Gerald C.

doi:10.1016/s0006-291x(88)81076-3

Cited by 77 publications

(8 citation statements)

References 10 publications

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“…Several studies have attempted to identify if transmembrane signals induced by agonist activation of PtdIns-4,5-P2-specific PLC are necessary cofactors for agonist-stimulable PLD and the conclusions reached are inconsistent. The role of physiological LCa2 ' 1, to regulate PLD is still controversial as the PtdCho-dependent PLD has been shown to be both ICa"1, sensitive (Anthes et al, 1989;Takai and Kanfer, 1979;Tettenborn and Mueller, 1988) and [Ca2+ I, insensitive (Domino et al, 1989;Martin, 1988;Martinson et al, 1989). Equally as controversial, PLD has been shown to be PKC dependent in endothelial cells (Martin et al, 1989) and granulocytes (Billah and Anthes, 19901, but not in platelets (Huang et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Platelet‐activating factor stimulates phosphatidic acid formation in cultured rat mesangial cells: Roles of phospholipase D, diglyceride kinase, and de novo phospholipid synthesis

Kester

1993

Journal Cellular Physiology

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Platelet-activating factor (PAF) stimulates phospholipase C (PLC)-induced hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2). Yet, PAF-stimulated diglycerides (DG) are still elevated at time points where inositol polyphosphates have returned to basal levels. Thus, other signal transduction pathways that hydrolyze phosphatidylcholine (PtdCho) or phosphatidylethanolamine (PtdEth) and form DG and phosphatidic acids (PA) through either PLC or phospholipase D (PLD) may also mediate PAF-stimulated cellular responses. Initially the effects of PAF upon 32P-PA generation in mesangial cells (MC) were assessed. PA formation may be indicative of several metabolic pathways including PLD and DG kinase activities as well as de novo phospholipid synthesis. PAF (10(-7) M) increased 32P-PA formation as early as 5 seconds and this elevation persisted up to 15 minutes. When MC were pretreated with the DG kinase inhibitor-R59022, PAF-induced 32P-PA formation was diminished at early but not late time points, demonstrating that the initial component of PA formation may be due, in part, to PLC activation and subsequent phosphorylation of DG. The reciprocal reaction, PA phosphohydrolase, which dephosphorylates PA to from DG was not stimulated by PAF, suggesting that the sustained elevation of DG induced by PAF is primarily a reflection of PLC. 3H-glycerol pulse-labeling experiments suggest that PAF also stimulates de novo phospholipid synthesis which also contributes to PA formation. Conclusive proof for PLD in the generation of PA was obtained by assessing the formation of 3H-phosphatidyl-ethanol (PEt) from 3H-alkyl-lyso-glycero phosphocholine (GPC) and exogenous ethanol. PAF stimulated alkyl-PEt generation in the presence but not the absence of 0.5% ethanol. Also, PAF induced a concomitant elevation of alkyl-PA at 15 minutes and this elevation of alkyl-PA was reduced when the cells were exposed to exogenous ethanol, reflecting the formation of PEt. Corroborating evidence suggests that PAF stimulates 3H-choline and 3H-ethanolamine release, suggesting that PtdCho and PtdEth are substrates for PLD. Thus, these data demonstrate that MC respond to PAF with elevated PLD and DG kinase activities as well as with an increased rate of de novo lipid synthesis which increases PA, a potential intracellular signal.

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Section: Discussionmentioning

confidence: 99%

Platelet‐activating factor stimulates phosphatidic acid formation in cultured rat mesangial cells: Roles of phospholipase D, diglyceride kinase, and de novo phospholipid synthesis

Kester

1993

Journal Cellular Physiology

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“…The role of physiological [Ca2+li to regulate phospholipase D is still controversial as the PtdCho-dependent phospholipase D has been shown to be both [Ca2'li-sensitive (Takai and Kanfer, 1979;Tettenhorn and Mueller, 1988;Anthes et al, 1989) and -insensitive (Martin 1988;Domino et al, 1989;Martinson et al, 1989). Equally as controversial, phospholipase D has been shown to be PKC-dependent in endothelial cells and granulocytes (Billah et al, 1988), but not in platelets (Huang et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Endothelin stimulates phosphatidic acid formation in cultured rat mesangial cells: Role of a protein kinase C‐regulated phospholipase D

Kester

Simonson

McDermott

et al. 1992

Journal Cellular Physiology

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We have previously reported that endothelin-1 stimulates phospholipase C-induced hydrolysis of phosphatidylinositol-4,5-bisphosphate. Other signal transduction pathways that hydrolyze alternative phospholipids through phospholipase D may also mediate endothelin-stimulated cellular responses. We initially evaluated endothelin-dependent generation of 32P-phosphatidic acid as an indirect indication of phospholipase D activity in rat mesangial cells. Endothelin (10(-7) M) induced an elevation of phosphatidic acid that was maximal at 15 min and persisted upward of 60 min. Pretreatment with the diacylglycerol-kinase inhibitor, R59022, did not reduce formation of endothelin-stimulated 32P-phosphatidic acid, demonstrating that the sequential actions of phospholipase C/diacylglycerol kinase do not contribute to endothelin-stimulated phosphatidic acid formation. We next conclusively identified a role for phospholipase D in the generation of phosphatidic acid by assessing the formation of 3H-phosphatidylethanol from 3H-alkyl lyso glycerophosphocholine and exogenous ethanol. Endothelin stimulated 3H-alkyl phosphatidylethanol formation in the presence but not the absence of 0.5% ethanol. Also, endothelin induced a concomitant elevation of 3H-alkyl-phosphatidic acid that was significantly reduced when the cells were exposed to exogenous ethanol, reflecting the formation of phosphatidylethanol. In addition, endothelin stimulated the release of 3H-choline and 3H-ethanolamine, demonstrating that additional phospholipids may serve as substrates for phospholipase D. Phorbol esters and synthetic diglycerides mimicked the effects of endothelin to stimulate phospholipase D and inhibitors of protein kinase C significantly reduced endothelin-stimulated phospholipase D. In addition, endothelin did not stimulate phosphatidylethanol formation in protein kinase C down-regulated cells. The calcium ionophore, ionomycin, did not stimulate phospholipase D and mesangial cells pretreated with BAPTA to chelate cytosolic calcium did not show a diminished endothelin-stimulated phospholipase D. Thus these data demonstrate that mesangial cells possess a protein kinase C-regulated phospholipase D activity that can be stimulated with endothelin.

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“…The first hints of a link between PKC and PLD came from early studies that showed that phorbol esters such as PMA could induce PC hydrolysis, resulting in the accumulation of PA and DAG [79][80][81][82]. Prior to the cloning of PLD and the production of recombinant enzymes for study, a variety of indirect approaches built the case for a link between PKC and PLD [57].…”

Section: Regulation Of Pld By Pkcmentioning

confidence: 99%

Protein kinase C and phospholipase D: intimate interactions in intracellular signaling

Becker

Hannun

2005

CMLS, Cell. Mol. Life Sci.

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Diacylglycerol (DAG) was discovered as a potent lipid second messenger with protein kinase C (PKC) as its major cellular target more than 25 years ago. There is increasing evidence of significant complexity within lipid signaling, and the classical DAG-PKC model no longer stands alone but is part of a larger bioactive lipid universe involving glycerolipids and sphingolipids. Multiple layers of regulation exist among PKC- and DAG-metabolizing enzymes such as phosphatidylcholine (PC)-specific phospholipase D, and cross-talk exists between the glycerolipid and sphingolipid pathways, with PKC at the center. Currently, there is intense interest in the question of whether DAG derived from PC can function as a lipid second messenger and regulate PKC analogous to DAG derived from phosphatidylinositol-4,5-bisphosphate (PIP2). To address these issues and incorporate DAG-PKC and other signaling pathways into an expanded view of cell biology, it will be necessary to go beyond the classical approaches and concepts.

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12-O-tetradecanoylphorbol-13-acetate activates phosphatidylethanol and phosphatidylglycerol synthesis by phospholipase D in cell lysates

Cited by 77 publications

References 10 publications

Platelet‐activating factor stimulates phosphatidic acid formation in cultured rat mesangial cells: Roles of phospholipase D, diglyceride kinase, and de novo phospholipid synthesis

Platelet‐activating factor stimulates phosphatidic acid formation in cultured rat mesangial cells: Roles of phospholipase D, diglyceride kinase, and de novo phospholipid synthesis

Endothelin stimulates phosphatidic acid formation in cultured rat mesangial cells: Role of a protein kinase C‐regulated phospholipase D

Protein kinase C and phospholipase D: intimate interactions in intracellular signaling

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