Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis

Kiss, Zoltán; Tomono, Masahiro

doi:10.1016/0005-2760(95)00148-6

Cited by 59 publications

(45 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we showed that lower concentrations of compound 609 exhibit co-mitogenic effects, which reinforces our previous conclusion that compound D 609 cannot be used as a specific inhibitor of phospholipase C [12]. However, the use of this compound in this work helped to clarify the absence of causal relationship between the mitogenic effects of ethanolamine analogues and phospholipid synthesis.…”

Section: Discussionsupporting

confidence: 89%

“…Recently, we have demonstrated that concentrations of compund D 609 which inhibit PtdCho-specific phospholipase C activity also inhibit phospholipase D activity [12]. Here we showed that lower concentrations of compound 609 exhibit co-mitogenic effects, which reinforces our previous conclusion that compound D 609 cannot be used as a specific inhibitor of phospholipase C [12].…”

Section: Discussionsupporting

confidence: 89%

“…Thus, ethanolamine analogues and choline phosphate potentiate the mitogenic effects of insulin through wortmannin-sensitive and-insensitive mechanisms, respectively. During this study we found that low (1-5 ~g/ml) concentrations of D 609, which do not modify phospholipase activities [12], can greatly enhance the mitogenic effect of insulin; this is shown in Fig. 2.…”

Section: Resultsmentioning

confidence: 63%

“…We have shown that at these concentrations compound D 609 also inhibits phospholipase D activity [12]. However, when we began to use compund D 609 to study the role of phospholipase activities in cell growth regulation, it turned out that at lower concentrations this compound exhibits mitogenic activity.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Kiss

Crilly

1996

FEBS Letters

Self Cite

View full text Add to dashboard Cite

Dimethylethanolamine (0.5-1 mM), added to serumstarved N1H 3T3 fibroblasts, stimulated DNA synthesis 11-32-fold, and it also greatly enhanced the relatively modest (15-20-fold) mitogenic effect of insulin. Ethanolamine and momomethylethanolamine alone had no effects on DNA synthesis, but they also enhanced the stimulatory effect of insulin, although less effectively than dimethylethanolamine did. Lower concentrations (2.5-5 ~tglml) of compound D 609 (tricyclo-9-yl-xanthogenate), which had no effects on phospholipase activities, synergistically enhanced the combined effects of ethanolamine analogs and insulin on DNA synthesis without affecting the synthesis of ethanolamine phospholipids. These results suggest that ethanolamine and its analogues, formed by phospholipase D-mediated hydrolysis of ethanolamine phospholipids, may have growth regulatory functions independent of their role as phospholipid precursors.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Section: Resultsmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Kiss

Crilly

1996

FEBS Letters

Self Cite

View full text Add to dashboard Cite

show abstract

“…2. There have been recent reports in which D609 was found to not only exert effects upon PC-PLC but also PLD (44,45) and PI-PLC (46,47). These results do not preclude the possible role of PC-PLC or PLD in MMP-13 protein expression.…”

Section: Discussionmentioning

confidence: 99%

Serotonin-induced MMP-13 Production Is Mediated via Phospholipase C, Protein Kinase C, and ERK1/2 in Rat Uterine Smooth Muscle Cells

Shum

Melendez

Jeffrey

2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Serotonin (5-hydroxytryptamine; 5-HT), acting via the 5-HT 2A receptor, up-regulates the transcription and production of interstitial collagenase (matrix metalloproteinase-13; MMP-13), a critical enzyme responsible for maintaining the integrity of the uterus, after parturition. Serotonin treatment of rat uterine myometrial smooth muscle cells induced inositol phosphate (IP) turnover, which was abolished by the 5-HT 2A receptorspecific antagonists ketanserin and spiperone. The phospholipase C (PLC) inhibitors U73122 and D609 attenuated serotonin-mediated-IP turnover with a corresponding inhibition of MMP-13 protein production. Subsequent recovery of both MMP-13 protein expression and IP generation was seen following the removal of D609. Protein kinase C (PKC) activators, the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol and phorbol myristate acetate (PMA), mimicked the effect of serotonin on MMP-13 protein expression; prolonged PMA treatment (which down-regulates PKC) lowered MMP-13 protein levels. The PKC-specific inhibitors bisindolylmaleimide I, calphostin C, CGP 41251, and the PKC␦-selective inhibitor rottlerin were able to suppress serotonin up-regulation of MMP-13. Furthermore, the mitogen-activated protein kinase kinase (MEK) inhibitor PD98059 blocked serotonin-dependent activation of p44/42 MAPK (pERK1/2), a downstream effector of PKC and also down-regulated MMP-13 protein expression. Similarly, calphostin C and rottlerin depressed activation of p44/42 MAPK. From these studies, serotonin, binding through the 5-HT 2A receptor, initiates a signaling cascade whereby stimulation of PLC leads to the activation of PKC and subsequently the ERK1/2 pathway, which ultimately results in MMP-13 production.The maintenance of the three-dimensional architecture of the mammalian uterus is carefully regulated during pregnancy and after parturition. Production of fibrillar collagens (Types I and III) is up-regulated 10-fold in the uterus during pregnancy (1, 2). These collagens possess a rigid superhelical structure, which is responsible for providing the tensile strength necessary to accommodate the force exerted by the growing fetus. After parturition, a precisely programmed non-necrotic and non-inflammatory process of connective tissue remodeling occurs, which results in the rapid and dramatic degradation of the collagen amassed and returns the uterus to reproductive competence (3). This transition is initiated by the enzyme interstitial collagenase (matrix metalloproteinase-13; MMP-13), 1 a member of the matrix metalloproteinase family. It acts as not only the rate-limiting step but also the committed step in the catalysis of the degradation of extracellular collagen (4, 5). The expression of MMP-13 occurs during postpartum involution and is not present either during the pregnancy or even within hours prior to parturition. The myometrial smooth muscle cell of the uterus has been identified not only as the source for MMP-13 (6) but also that of its natural substrate, collagen (7). Thus, the myometrial smooth muscle...

show abstract

Mechanisms of protein kinase D activation in response to P2Y₂ and P2X7 receptors in primary astrocytes

Carrasquero

Delicado

Sánchez‐Ruiloba

et al. 2010

Glia

View full text Add to dashboard Cite

Protein kinase D (PKD) is a family of serine/threonine kinases that can be activated by many stimuli via protein kinase C in a variety of cells. This is the first report where PKD activation and localization is studied in glial cells. Herein, we demonstrate that P2Y(2) and P2X7 receptor stimulation of primary rat cerebellar astrocytes rapidly increases PKD1/2 phosphorylation and activity. P2Y(2) receptor response evokes a PKD1/2 activation that is dependent on a pertussis toxin-insensitive G protein, phospholipase C (PLC)-mediated generation of diacylglycerol, and protein kinase C. This mechanism is similar to the one described for other G-protein coupled receptors. In contrast, the way the ionotropic P2X7 receptor activates PKD1/2 is significantly different. Importantly, this response is not dependent on calcium entry, but depends on the activity of several phospholipases, including phosphoinositide-phospholipase C (PI-PLC), phosphatidylcholine-phospholipase C (PC-PLC) and also phospholipase D (PLD). Immunoblot and confocal microscopy analysis show that PKD1/2 activation by nucleotides is transient. The active kinase first moves to and concentrates in certain plasma membrane domains. Then, phosphorylated-PKD1/2 translocates to intracellular vesicles, where it remains active. All together, our results open the perspective of PKD1/2 being involved in many physiological functions where nucleotides play important roles not only in astrocytes but in other cell types bearing these receptors.

show abstract

Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis

Cited by 59 publications

References 18 publications

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Serotonin-induced MMP-13 Production Is Mediated via Phospholipase C, Protein Kinase C, and ERK1/2 in Rat Uterine Smooth Muscle Cells

Mechanisms of protein kinase D activation in response to P2Y₂ and P2X7 receptors in primary astrocytes

Contact Info

Product

Resources

About

Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis

Cited by 59 publications

References 18 publications

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Ethanolamine analogues stimulate DNA synthesis by a mechanism not involving phosphatidylethanolamine synthesis

Serotonin-induced MMP-13 Production Is Mediated via Phospholipase C, Protein Kinase C, and ERK1/2 in Rat Uterine Smooth Muscle Cells

Mechanisms of protein kinase D activation in response to P2Y2 and P2X7 receptors in primary astrocytes

Contact Info

Product

Resources

About

Mechanisms of protein kinase D activation in response to P2Y₂ and P2X7 receptors in primary astrocytes