Antitumoral activity of a xanthate compound. I. Cytotoxicity studies with neoplastic cell lines in vitro.
AuthorsSchick HD, Amtmann E, Berdel WE, Danhauser-Riedl S, Reichert A, Steinhauser G, Rastetter J, Sauer G
JournalCancer Lett
PubMed ID2752383
Xanthate derivatives were shown previously to display antitumor activity against transformed fibroblasts and lymphoma cells in combination with monocarboxylic acids [1]. Various malignant cell lines of human origin were treated in vitro to explore the range of antitumoral activity of the compounds. The combination of tricyclodecan-9-yl-xanthogenate (D 609) with undecanoic ... More
Selective killing of tumor cells by xanthates.
AuthorsAmtmann E, Sauer G
JournalCancer Lett
PubMed ID3594421
Xanthate derivatives of primary alcohols with antiviral properties exert, in combination with monocarboxylic C11 or C12 acids a pronounced anti-tumor activity in vitro and in vivo. Tricyclodecan-9-yl-xanthogenate (D609) or cyclododecyl xanthogenate (D435) when administered together with either undecanoic or dodecanoic acid to various transformed animal and human tumor cells (displaying ... More
Bradykinin-stimulated phosphatidylcholine hydrolysis in airway smooth muscle: the role of Ca2+ and protein kinase C.
AuthorsPyne S, Pyne NJ
JournalBiochem J
PubMed ID7487907
'The regulation of phosphatidylcholine (PtdCho) hydrolysis by Ca2+ and protein kinase C (PKC) was measured in [3H]palmitate-labelled cultured guinea-pig airway smooth-muscle cells as phosphatidylbutanol ([3H]PtdBut) and phosphatidate ([3H]PtdOH) formation in the presence of butanol. The former is a direct measure of phospholipase D (PLD) activity, whereas the latter, in airway ... More
Fas/Apo-1 activates nuclear factor kappa B and induces interleukin-6 production.
AuthorsRensing-Ehl A, Hess S, Ziegler-Heitbrock HW, Riethmüller G, Engelmann H
JournalJ Inflamm
PubMed ID8597871
'Fas antigen/Apo-1 (Fas) and the p55 tumor necrosis factor receptor (TNF-R) are two related cell surface molecules that induce apoptosis in susceptible cells. With regard to their cytoplasmic homology region, we investigated whether Fas like the TNF-R activates nuclear factor kappa B (NF-kappa B), using human SV80 fibroblasts transfected with ... More
Inhibitors of spasmogen-induced Ca2+ channel suppression in smooth muscle cells from small intestine.
AuthorsUnno T, Beech DJ, Komori S, Ohashi H
JournalBr J Pharmacol
PubMed ID9831900
'1. Whole-cell patch-clamp recordings were made from smooth muscle cells isolated from the longitudinal muscle layer of guinea-pig ileum. Carbachol (acting at muscarinic receptors) or histamine (acting at H1 histamine receptors) suppressed Ca2+ channel current. The effect of either agonist had an initial transient component followed by a sustained component. ... More
HDL3 stimulates multiple signaling pathways in human skin fibroblasts.
AuthorsWalter M, Reinecke H, Nofer JR, Seedorf U, Assmann G
JournalArterioscler Thromb Vasc Biol
PubMed ID7583579
'The influence of HDL3 on phospholipid breakdown was examined in human skin fibroblasts. HDL3 elicited phosphatidylcholine (PC) and phosphatidylinositol (PI) turnover and activated multiple phospholipases. In [14C]lyso-PC-labeled or [14C]choline (Cho)-labeled cells, a biphasic activation of PC-specific phospholipase D (PLD) with peak maxima 30 to 60 seconds and 5 to 7 ... More
Tumor necrosis factor induces necrosis of human carcinoma xenografts in the presence of tricyclodecan-9-yl-xanthogenate and lauric acid.
AuthorsAmtmann E, Sauer G
JournalInt J Cancer
PubMed ID2141005
'Recombinant human tumor necrosis factor (rh TNF) when administered intravenously together with the phospholipase C inhibitor tricyclodecan-9-yl-xanthogenate (D609) and lauric acid (C12), leads to the partial regression of various human tumor transplants in athymic mice. Extensive necrosis occurred after a single intravenous infusion, with no detectable side effects. TNF-mediated cytotoxicity ... More
DNA and RNA virus species are inhibited by xanthates, a class of antiviral compounds with unique properties.
AuthorsSauer G, Amtmann E, Melber K, Knapp A, Müller K, Hummel K, Scherm A
JournalProc Natl Acad Sci U S A
PubMed ID6328507
'Various DNA and RNA virus species are inhibited by xanthate compounds at concentrations that leave the mitotic activity of uninfected cells unimpaired. The concentration of tricyclodecan -9-yl- xanthogenate that reduces the yield of herpes simplex virus types 1 and 2 by 50% is between 4.5 and 33 microM. The replication ... More
Tumor prevention by a xanthate compound in experimental mouse-skin tumorigenesis.
AuthorsFürstenberger G, Amtmann E, Marks F, Sauer G
JournalInt J Cancer
PubMed ID2494119
'The antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609), which is an inhibitor of protein kinase C activation, has been used for tumor prevention in vivo. When applied chronically together with 12-O-tetradecanoylphorbol-13-acetate (TPA) in the classic initiation-promotion mouse-skin model, D609 prevented tumor induction in a dose-dependent manner. At the concentration that inhibited ... More
Relationships between phosphatidylcholine-specific phospholipase C and integrins in cell-substratum adhesion and apoptosis in vascular endothelial cells.
AuthorsMiao JY, Araki S, Hayashi H
JournalEndothelium
PubMed ID9588821
'In order to understand the mechanism by which VEC control cell-substratum adhesion and apoptosis, we investigated relationships between PC-PLC and the integrins that are normally expressed in VEC. We found that promotion of cell-substratum adhesion by suppression of PC-PLC was almost completely blocked by a monoclonal antibody (mAb) against integrin ... More
Mechanistic aspects of the synergistic antiviral effect of xanthates and monocarbonic acids.
AuthorsMusic L, Müller-Decker K, Amtmann E, Sauer G
JournalBiochem Pharmacol
PubMed ID2545206
'The xanthate tricyclodecan-9-yl-xanthogenate (D609) displays antiviral and antitumoral properties that are inversely proportional in vitro to the serum concentration. Accordingly, it has been found that D609 binds to serum albumin. Recently, we have reported that D609, in combination with undecanoic acid, has a synergistic antiviral effect, which appears, as shown ... More
Induction of nitric oxide synthase activity in phagocytic cells inhibited by tricyclodecan-9-yl-xanthogenate (D609).
AuthorsTschaikowsky K, Meisner M, Schönhuber F, Rügheimer E
JournalBr J Pharmacol
PubMed ID7532078
'1. The synthesis of nitric oxide (NO) by immune-stimulated murine phagocytic cells (J774) and the modulation of this synthesis by tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), was investigated. D609 dose-dependently suppressed production of NO, as measured by the release of nitrite and nitrate, in response to ... More
Adenosine acts as an endogenous modulator of IL-2-dependent proliferation of cytotoxic T lymphocytes.
AuthorsAntonysamy MA, Moticka EJ, Ramkumar V
JournalJ Immunol
PubMed ID7673697
'CTLL-2 cells are a clone of CTL that are dependent on IL-2 for proliferation. In addition to various cytokine receptors, we observed that these cells express three subtypes of adenosine receptors (ARs). In an initial attempt to delineate the functions of these receptors in CTLL-2 cells, we tested their role ... More
Inhibitors of basement membrane collagen synthesis prevent endothelial cell alignment in matrigel in vitro and angiogenesis in vivo.
AuthorsHaralabopoulos GC, Grant DS, Kleinman HK, Lelkes PI, Papaioannou SP, Maragoudakis ME
JournalLab Invest
PubMed ID7526036
'BACKGROUND: The formation of a basement membrane is the last step in the development of a new blood vessel. Matrigel, a laminin-rich reconstituted basement membrane matrix induces the differentiation of endothelial cells into capillary-like structures. EXPERIMENTAL DESIGN: The effect of inhibitors of basement membrane collagen synthesis, tricyclodecan-9-yl xanthate (D609) and ... More
Antisense oligonucleotides targeting protein kinase C-alpha, -beta I, or -delta but not -eta inhibit lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages: involvement of a nuclear factor kappa B-dependent mechanism.
AuthorsChen CC, Wang JK, Lin SB
JournalJ Immunol
PubMed ID9834107
'The signaling pathway for protein kinase C (PKC) activation and the role of PKC isoforms in LPS-induced nitric oxide (NO) release were studied in RAW 264.7 macrophages. The tyrosine kinase inhibitor genestein attenuated LPS-induced NO release and inducible nitric oxide synthase (iNOS) expression, as did the phosphoinositide-specific phospholipase C (PI-PLC) ... More
Tumor necrosis factor-alpha autoregulates interleukin-6 synthesis via activation of protein kinase C. Function of sphingosine 1-phosphate and phosphatidylcholine-specific phospholipase C.
AuthorsKozawa O, Suzuki A, Kaida T, Tokuda H, Uematsu T
JournalJ Biol Chem
PubMed ID9312119
'We investigated the mechanism of interleukin-6 (IL-6) synthesis induced by tumor necrosis factor-alpha (TNF) in osteoblast-like MC3T3-E1 cells. TNF stimulated the synthesis of IL-6 dose dependently in the range between 1 and 30 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the TNF-induced synthesis of ... More
Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices.
AuthorsUndie AS
JournalBrain Res
PubMed ID9878788
'Dopamine receptor-coupled stimulation of inositol phosphate formation has been characterized extensively, but little is known about the diacylglycerol arm of this dual-signaling pathway. This study examined several parameters of cytidine diphosphate-diacylglycerol (CDP-DG) accumulation as an index of agonist-stimulated DG formation. Rat brain slices pre-labeled with 5-[3H]cytidine were incubated with various ... More
Protein kinase C activation by interleukin (IL)-1 limits IL-1-induced IL-6 synthesis in osteoblast-like cells: involvement of phosphatidylcholine-specific phospholipase C.
AuthorsKozawa O, Suzuki A, Tokuda H, Kaida T, Uematsu T
JournalJ Cell Biochem
PubMed ID9328844
'We investigated the regulatory mechanism of interleukin-6 (IL-6) synthesis induced by interleukin-1 (IL-1) in osteoblast-like MC3T3-E1 cells. IL-1 stimulated the secretion of IL-6 in a dose-dependent manner in the range between 0.1 and 100 ng/ml. Staurosporine and calphostin C, inhibitors of protein kinase C (PKC), significantly enhanced the IL-1-induced secretion ... More
Compartmentalized production of ceramide at the cell surface.
AuthorsLiu P, Anderson RG
JournalJ Biol Chem
PubMed ID7592974
'Ceramide produced by the hydrolysis of sphingomyelin is an important cellular intermediate in hormone action. Here, we present evidence that interleukin 1 beta (IL-1 beta) binding to normal human fibroblasts initiates a lipid messenger cascade that takes place in a sphingomyelin-rich plasma membrane domain with the characteristics of caveolae. Hormone ... More
Separation of integrin-dependent adhesion from morphological changes based on differential PLC specificities.
AuthorsWooten DK, Teague TK, McIntyre BW
JournalJ Leukoc Biol
PubMed ID9886255
'In normal lymphocytes an inside-out signal up-regulating integrin adhesion is followed by a ligand-mediated outside-in cell spreading signal. Protein kinase C (PKC) inhibition blocks lymphocyte adherence to and spreading on fibronectin. In contrast, putative PLC inhibitors yield distinct differences with respect to adhesion and morphology. The phosphatidylinositol-specific phospholipase C (PLC) ... More
Systemic treatment of a human epidermoid non-small cell lung carcinoma xenograft with a xanthate compound causes extensive intratumoral necrosis.
AuthorsSauer G, Amtmann E, Hofmann W
JournalCancer Lett
PubMed ID2170004
'Therapeutic effects were obtained after systemic treatment of athymic mice bearing an epidermoid non-small cell human lung carcinoma (NSCLC) xenograft with tricyclodecan-9-yl xanthogenate (D609) and the potassium salt of a fatty (dodecanoic) acid. Extensive intratumoral necrosis was observed 3 days after the treatment.' ... More
Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C?
AuthorsLuberto C, Hannun YA
JournalJ Biol Chem
PubMed ID9603970
'Sphingomyelin synthase (SMS), an enzyme involved in sphingomyelin (SM) and ceramide metabolism, can potentially regulate, in opposite directions, the levels of ceramide and diacylglycerol. In this study SMS activity was investigated in normal and SV40-transformed human lung fibroblasts (WI38). The addition of [3H]C2-ceramide to cells resulted in a time-dependent formation ... More
Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule-1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-alpha.
AuthorsWeber C, Erl W, Pietsch A, Danesch U, Weber PC
JournalArterioscler Thromb Vasc Biol
PubMed ID7538427
'Incorporation of the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) but not eicosapentaenoic acid or n-6 arachidonic acid into human umbilical vein endothelial cell (HUVEC) phospholipids dose-dependently reduced tumor necrosis factor-alpha (TNF-alpha)-induced surface expression of vascular cell adhesion molecule-1 (VCAM-1). In parallel, DHA inhibited TNF-alpha-stimulated monocytic U937 cell adhesion to ... More
Synergistic antiviral effect of xanthates and ionic detergents.
AuthorsAmtmann E, Müller-Decker K, Hoss A, Schalasta G, Doppler C, Sauer G
JournalBiochem Pharmacol
PubMed ID3034292
'Xanthate compounds have been shown to exhibit antiviral activity against various DNA and RNA viruses under acidic pH conditions. It is now possible to utilize the unique broad range antiviral spectrum of these compounds under physiological pH conditions (pH 7.4) by simultaneous administration of certain ionic detergents. When used in ... More
Inhibition of c-fos transcription and phosphorylation of the serum response factor by an inhibitor of phospholipase C-type reactions.
AuthorsSchalasta G, Doppler C
JournalMol Cell Biol
PubMed ID2169025
Phospholipase C activity is necessary for transcriptional c-fos activation by providing diacylglycerol as an activator of protein kinase C. We found that transcriptional activation of c-fos and the phosphorylation of its major transcription factor were inhibited by tricyclodecan-9-yl xanthogenate, which blocks phospholipase C-type reactions. Transcription of the c-ras and beta-actin ... More
Basement membrane biosynthesis as a target to tumor therapy.
AuthorsMaragoudakis ME, Missirlis E, Sarmonika M, Panoutsacopoulou M, Karakiulakis G
JournalJ Pharmacol Exp Ther
PubMed ID1690295
Tricyclodecan-9-yl-xanthate (D609) was identified as an agent that caused selective killing of tumor cells by an unknown mechanism of action. We report an inhibition by D609 of basement membrane collagen biosynthesis in the chick chorioallantoic membrane system in vitro. In the same system in vivo D609 inhibits angiogenesis. Also treatment ... More
Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase C-mediated phosphatidylethanolamine hydrolysis.
AuthorsKiss Z, Tomono M
JournalBiochim Biophys Acta
PubMed ID7492608
Tricyclodecan-9-yl-xanthogenate (compound D609) has recently been used in various cellular systems to specifically inhibit the activity of phosphatidylcholine (PtdCho)-directed phospholipase C (PLC). Here we show that in intact NIH 3T3 fibroblasts, concentrations of D609 (35 to 50 micrograms/ml) which have been used to inhibit PLC activity also significantly inhibit phorbol ... More
Interruption of growth signal transduction by an antiviral and antitumoral xanthate compound.
AuthorsMüller-Decker K, Doppler C, Amtmann E, Sauer G
JournalExp Cell Res
PubMed ID2839351
The binding of growth factors to the cellular receptors elicits the phosphorylation of proteins which transmit growth signals to the nucleus [E. Rozengurt (1986) Science 234, 161-166]. Both the tyrosine-specific kinase (growth factor receptor) and the threonine-serine phosphorylating protein kinase C (pkC) become activated upon binding of the epidermal growth ... More
Activation of mitogen-activated protein kinase by the nociceptin receptor expressed in Chinese hamster ovary cells.
AuthorsFukuda K, Shoda T, Morikawa H, Kato S, Mori K
JournalFEBS Lett
PubMed ID9256237
Activation of the nociceptin receptor stably expressed in Chinese hamster ovary cells induced a transient mitogen-activated protein kinase (MAPK) activation, via pertussis toxin-sensitive G-proteins. The nociceptin receptor-mediated MAPK activation was partially blocked by down-regulation or inhibition of protein kinase C, and suppressed by pretreatment with a phosphatidylcholine-specific phospholipase C inhibitor, ... More
Antiviral effects of xanthate D609 on the human respiratory syncytial virus growth cycle.
AuthorsVillanueva N, Navarro J, Cubero E
JournalVirology
PubMed ID1994569
The antiviral compound tricyclo-decan-9-yl-xanthogenate (D609) inhibits respiratory syncytial (RS) virus growth in human epithelial (Hep 2) cells. D609 treatment resulted in a decrease in the accumulation of viral proteins, in the phosphorylation of the viral phosphoprotein, and in the amount of extracellular antigens and infectious particles. The relative accumulation of ... More
Inhibition of HIV-1 replication by an antiviral xanthate compound in vitro.
AuthorsMellert W, Amtmann E, Erfle V, Sauer G
JournalAIDS Res Hum Retroviruses
PubMed ID3365357
The antiviral xanthate compound tricyclodecan-9-yl-xanthogenate (code name D609) is capable of inhibiting DNA and RNA viruses in vitro. It can also inhibit the shedding of infectious HIV into the tissue culture medium from chronically infected lymphoma cells (KE37-III) as shown by infectivity assays and Western blots of the supernatant. HIV-specific ... More
Antiviral xanthate causes conformational changes in simian virus 40 DNA and chromatin.
AuthorsWaldeck W
JournalOncology
PubMed ID2156205
Xanthates possess a wide antiviral and antitumoral spectrum. Treatment of simian virus 40 (SV40)-infected cells with tricyclo-decan-9-yl-xanthate (D609) reduces transcription and replication. Concomitantly, we observed condensation of the SV40 minichromosomes after addition of D609 to the tissue culture. The structural change of the viral chromatin was measured as an increase ... More
Stimulation of DNA synthesis in untransformed cells by the antiviral and antitumoral compound tricyclodecan-9-yl-xanthogenate (D609).
AuthorsKiss Z, Crilly KS, Chung T
JournalBiochem Pharmacol
PubMed ID9586966
The antiviral and antitumor xanthate compound tricyclodecan-9-yl-xanthogenate (D609) is best known for its inhibitory effect on phosphatidylcholine-specific phospholipase C activity. Now we report that in NIH 3T3 cells, but not in several transformed cell types tested, D609 stimulated DNA synthesis when phosphocholine (PCho), insulin, or ATP was also present. Maximal ... More
Inhibition of the phosphorylation of the regulatory non-structural protein of vesicular stomatitis virus by an antiviral xanthate compound.
AuthorsMüller-Decker K, Amtmann E, Sauer G
JournalJ Gen Virol
PubMed ID2447222
The growth of vesicular stomatitis virus (VSV) can be inhibited by the antiviral compound tricyclo-decane-9-yl-xanthogenate (D609). On analysing the antiviral mechanism we found no effect on the primary transcription of infecting VSV genomes. In contrast, the processes of replication and transcription during late stages of infection were inhibited. Despite the ... More
Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: inhibition of a phospholipase C-type reaction.
AuthorsMüller-Decker K
JournalBiochem Biophys Res Commun
PubMed ID2751648
The effect of tricyclodecan-9-yl-xanthogenate on the phorbolester TPA induced changes in phosphatidylcholine metabolism was investigated. In the simultaneous presence of the xanthate TPA failed to stimulate the metabolic [32P] turnover of the major phospholipids. The precursor molecule [3H] choline was incorporated into phosphatidylcholine after pulse labeling in TPA/D609-treated cells. Thus, ... More
TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown.
In this paper, we describe a phospholipid transmission pathway mediating tumor necrosis factor (TNF) activation of the nuclear transcription factor kappa B (NF-kappa B). Central to this TNF signaling route is the second messenger-like molecule ceramide, which is generated by sphingomyelin (SM) breakdown catalyzed by a sphingomyelinase (SMase). SMase activation ... More
Phosphatidylcholine-specific phospholipase C regulates glutamate-induced nerve cell death.
AuthorsLi Y, Maher P, Schubert D
JournalProc Natl Acad Sci U S A
PubMed ID9636222
Phosphatidylcholine-specific phospholipase C (PC-PLC) is a necessary intermediate in transducing apoptotic signals for tumor necrosis factor and Fas/Apo-1 ligands in nonneuronal cells. The data presented here show that PC-PLC also is required in oxidative glutamate-induced programmed cell death of both immature cortical neurons and a hippocampal nerve cell line, HT22. ... More
Inflammatory activation of arachidonic acid signaling in murine P388D1 macrophages via sphingomyelin synthesis.
AuthorsBalsinde J, Balboa MA, Dennis EA
JournalJ Biol Chem
PubMed ID9252342
Ceramide has emerged as an important lipid messenger for many cellular processes triggered via surface receptors. In the present study, inflammatory activation of P388D1 macrophages with bacterial lipopolysaccharide (LPS) and platelet-activating factor (PAF) stimulated a transient accumulation of ceramide. Moreover, cell-permeable ceramide mimicked LPS/PAF in triggering arachidonate mobilization in these ... More
Phosphatidylcholine-specific phospholipase inhibitor D609 differentially affects MAP kinases and immediate-early genes in PC12 cells.
AuthorsKahle PJ, Shooter EM, Johnson RM, Verity AN
JournalCell Signal
PubMed ID9692675
The effects of tricyclodecan-9-yl xanthogenate (D609), an inhibitor of phosphatidylcholine-specific phospholipases, on PC12 cells were investigated. D609 repressed nerve growth factor (NGF)-mediated induction of c-fos mRNA with an IC50 approximately 50 microg/ml. Interestingly, maximal c-fos-suppressing doses of D609 did not affect activity of extracellular signal-regulated kinases. Surprisingly, D609 enhanced the ... More
Reversion of bovine papillomavirus-induced transformation and immortalization by a xanthate compound.
AuthorsAmtmann E, Müller K, Knapp A, Sauer G
JournalExp Cell Res
PubMed ID2998840
Bovine papilloma virus-transformed hamster embryo fibroblasts (HEF-BPV) reacted to exposure to tricyclodecan-9-yl-xanthogenate (D609) with immediate reversion to the growth kinetics and the flat morphology of the untransformed parental cells. After six population doublings in the presence of D609, clones which displayed an untransformed morphology in the absence of D609 arose ... More
Modulation of mouse endotoxin shock by inhibition of phosphatidylcholine-specific phospholipase C.
AuthorsTschaikowsky K, Schmidt J, Meisner M
JournalJ Pharmacol Exp Ther
PubMed ID9580629
During Gram-negative bacterial infections, lipopolysaccharide (LPS) interacts with monocyte/macrophage receptors, resulting in a host defense response. Activation of intracellular signal transduction pathways implicating various protein kinase and phospholipases is crucial in activating the transcription of genes encoding proinflammatory cytokines and inducible nitric oxide synthase (iNOS). In this article, we demonstrate ... More
Daunorubicin- and mitoxantrone-triggered phosphatidylcholine hydrolysis: implication in drug-induced ceramide generation and apoptosis.
AuthorsBettaïeb A, Plo I, Mansat-De Mas V, Quillet-Mary A, Levade T, Laurent G, Jaffrézou JP
JournalMol Pharmacol
PubMed ID9882705
Several studies have suggested that diacylglycerol can affect the induction of apoptosis induced by toxicants and ceramide. The present study demonstrates that clinically relevant concentrations of the chemotherapeutic drugs daunorubicin and mitoxantrone (0.2-1 microM) transiently stimulated concurrently with sphingomyelin-derived ceramide generation and diacylglycerol and phosphorylcholine production within 4 to 10 ... More
Evidence for involvement of phosphatidylcholine-phospholipase C and protein kinase C in transforming growth factor-beta signaling.
AuthorsHalstead J, Kemp K, Ignotz RA
JournalJ Biol Chem
PubMed ID7775410
Transforming growth factor-beta (TGF-beta) is a multifunctional peptide that elicits a wide variety of responses in cells. TGF-beta binds to cell surface receptors that contain cytoplasmic serine/threonine kinase domains. Here we provide evidence that both phospholipase C and protein kinase C (PKC) are involved in the TGF-beta activation of transcription ... More
Phosphatidylcholine-specific phospholipase C inhibitor, tricyclodecan-9-yl xanthogenate (D609), increases phospholipase D-mediated phosphatidylcholine hydrolysis in UMR-106 osteoblastic osteosarcoma cells.
AuthorsSingh AT, Radeff JM, Kunnel JG, Stern PH
JournalBiochim Biophys Acta
PubMed ID11018472
Our previous studies have shown that parathyroid hormone (PTH) stimulates phosphatidylcholine (PC) hydrolysis by phospholipase D (PLD) and transphosphatidylation in UMR-106 osteoblastic cells. To determine whether phospholipase C (PLC) is also involved in the PTH-mediated PC hydrolysis, we used the inhibitor, tricyclodecan-9-yl xanthogenate (D609), a putatively selective antagonist of this ... More
Suppression of apoptosis by inhibition of phosphatidylcholine-specific phospholipase C in vascular endothelial cells.
AuthorsMiao JY, Kaji K, Hayashi H, Araki S
JournalEndothelium
PubMed ID9588815
In order to clarify the role of phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of apoptosis in vascular endothelial cells (VEC), we investigated the effects of D609, a specific inhibitor of PC-PLC, on apoptosis that was induced by deprivation of fibroblast growth factor (FGF) and serum and also by rattlesnake ... More
Effects of phospholipase C inhibitors on Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by alpha 1A- and alpha 2A-adrenoceptors in rat portal vein myocytes.
AuthorsMacrez-Leprêtre N, Morel JL, Mironneau J
JournalBiochem Biophys Res Commun
PubMed ID8573150
The ability of phospholipase C inhibitors to inhibit Ca2+ channel stimulation and Ca2+ release from intracellular stores evoked by norepinephrine in single rat portal vein myocytes was investigated in the aim of identifying the type of phospholipase C involved in the transduction pathways activated by alpha 1A- and alpha 2A-adrenoceptors. ... More
Validation of collagenous protein synthesis as an index for angiogenesis with the use of morphological methods.
AuthorsMaragoudakis ME, Haralabopoulos GC, Tsopanoglou NE, Pipili-Synetos E
JournalMicrovasc Res
PubMed ID8538501
A method providing a biochemical index for the evaluation of promoters or inhibitors of angiogenesis in the chick chorioallantoic membrane (CAM) is here described and validated. This method is based on the determination of collagenous protein synthesis which takes place during new vessel formation. Validation was done by comparing collagenous ... More
IkappaBalpha degradation and nuclear factor-kappaB DNA binding are insufficient for interleukin-1beta and tumor necrosis factor-alpha-induced kappaB-dependent transcription. Requirement for an additional activation pathway.
AuthorsBergmann M, Hart L, Lindsay M, Barnes PJ, Newton R
JournalJ Biol Chem
PubMed ID9506955
Two closely related IkappaBalpha kinases as well as the upstream kinase, NIK, which integrates interleukin-1beta (IL-1beta)- and tumor necrosis factor (TNF)-alpha-dependent activation of the transcription factor NF-kappaB have recently been described. However, in this emerging pathway the role of previously identified components of cytokine-induced NF-kappaB activation, namely phosphatidylcholine-specific phospholipase C ... More
A phosphatidylcholine phospholipase C inhibitor, D609, blocks interleukin-3 (IL-3)-induced bcl-2 expression but not c-myc expression in human IL-3-dependent cells.
AuthorsMufson RA, Gubina E, Rinaudo M, Baxter G
JournalExp Cell Res
PubMed ID9596995
Activation of the interleukin-3 (IL-3) receptor is required for the induction of cell proliferation and suppression of apoptosis in primitive hematopoietic progenitor cells. A rapid activation of tyrosine kinases and a phosphatidylcholine-specific phospholipase C has been observed in these cells in response to IL-3. The signal transduction cascades regulating cell ... More
Pituitary adenylate cyclase activating polypeptide induces multiple signaling pathways in rat peritoneal mast cells.
AuthorsSeebeck J, Kruse ML, Schmidt-Choudhury A, Schmidtmayer J, Schmidt WE
JournalEur J Pharmacol
PubMed ID9716372
Pituitary adenylate cyclase activating polypeptide (PACAP) is a high-affinity ligand for at least two types of G-protein coupled receptors, the PACAP type 1 and type 2 receptor. In this study it is demonstrated that the C-terminal PACAP-fragment PACAP(6-27) stimulates serotonin release from rat peritoneal mast cells with higher potency (EC50: ... More
Evidence for cell surface and internal phospholipase activity in ascidian eggs.
AuthorsGoode CA, Gamboa-Pinto AJ, Cruz R, Gough LL, Lund CV, Lambert CC
JournalDev Growth Differ
PubMed ID9338601
Upon fertilization, ascidian eggs release a cell surface glycosidase used in the block to polyspermy and undergo cortical contractions resulting from increased intracellular calcium levels. The glycosidase is released by fertilization, calcium ionophores or added phospholipase C (PLC) activity. The PLC inhibitor D609 blocks glycosidase release. Intact Ascidia ceratodes eggs ... More
CD40 function in nonhematopoietic cells. Nuclear factor kappa B mobilization and induction of IL-6 production.
AuthorsHess S, Rensing-Ehl A, Schwabe R, Bufler P, Engelmann H
JournalJ Immunol
PubMed ID7594457
CD40 is a member of the TNF receptor family that was first characterized as an important T-B cell interaction molecule. This receptor is also expressed on many other cell types, including normal basal epithelium, carcinomas, and transformed cell lines. The functions of CD40 in non-B cells are largely unknown. Our ... More
Phosphatidylcholine-specific phospholipase C regulates thapsigargin-induced calcium influx in human lymphocytes.
AuthorsNofer JR, Tepel M, Walter M, Seedorf U, Assmann G, Zidek W
JournalJ Biol Chem
PubMed ID9407064
The involvement of phosphatidylcholine-specific phospholipase C (PC-PLC) and D (PC-PLD) in the regulation of the thapsigargin-induced Ca2+ increase was investigated. Pretreatment of human lymphocytes with the PC-PLC inhibitors D609 or U73122 enhanced the thapsigargin-induced Ca2+ influx. By contrast, no effect was observed in the presence of phospholipase D inhibitor butanol. ... More
Caspase-dependent ceramide production in Fas- and HLA class I-mediated peripheral T cell apoptosis.
AuthorsGenestier L, Prigent AF, Paillot R, Quemeneur L, Durand I, Banchereau J, Revillard JP, Bonnefoy-Bérard N
JournalJ Biol Chem
PubMed ID9478956
We recently demonstrated that the engagement of HLA class I alpha1 domain induced Fas-independent apoptosis in human T and B lymphocytes. We analyzed the signaling pathway involved in HLA class I-mediated apoptosis in comparison with Fas (APO-1, CD95)-dependent apoptosis. The mouse mAb90 or the rat YTH862 monoclonal antibodies which bind ... More
Rapid activation of sodium-proton exchange and extracellular signal-regulated protein kinase in fibroblasts by G protein-coupled 5-HT1A receptor involves distinct signalling cascades.
AuthorsGarnovskaya MN, Mukhin Y, Raymond JR
JournalBiochem J
PubMed ID9461547
These experiments tested the hypothesis that signalling elements involved in the activation of the extracellular signal-regulated protein kinase (ERK) mediate rapid activation of sodium-proton exchange (NHE) in fibroblasts when both signals are initiated by a single G protein-coupled receptor, the 5-HT1A receptor. Similarities between the two processes were comparable concentration-response ... More
Experimental treatment of equine sarcoid using a xanthate compound and recombinant human tumour necrosis factor alpha.
AuthorsOtten N, Marti E, Söderström C, Amtmann E, Burger D, Gerber H, Lazary S
JournalZentralbl Veterinarmed A
PubMed ID7653114
A xanthate compound with antiviral and antitumoural activities, tricyclodecan-9-yl-xanthogenate (D609) in combination with the potassium salt of the lauric acid (KC12) and, in a further investigation, the above-mentioned substances together with recombinant human TNF alpha (rh-TNF alpha), were tested on equine sarcoid tumours for therapeutic efficacy. A pilot investigation on ... More
The antiviral xanthate compound D609 inhibits herpes simplex virus type 1 replication and protein phosphorylation.
AuthorsWalro DG, Rosenthal KS
JournalAntiviral Res
PubMed ID9330762
The mechanism of antiviral action of tricyclodecan-9-yl-xanthogenate (D609) was investigated in vitro. D609 inhibited herpes simplex virus type 1 (HSV-1) replication without apparent cytotoxicity. It reduced phosphorylation of virus-infected cell polypeptides and inhibited the HSV-1 encoded protein kinase (US3 PK) and, to a lesser extent, cellular protein kinase C in ... More
Angiotensin II-mediated activation of L-type calcium channels involves phosphatidylinositol hydrolysis-independent activation of protein kinase C in rat portal vein myocytes.
AuthorsMacrez-Leprêtre N, Morel JL, Mironneau J
JournalJ Pharmacol Exp Ther
PubMed ID8768693
The action of angiotensin II (ANG II) was studied in single myocytes from rat portal vein, in which the cytoplasmic Ca++ concentration was estimated by emission from fluorescent dyes and the Ca++ channel current was measured with the whole-cell mode of the patch-clamp technique. ANG II stimulated Ca++ channel current ... More
Lysophosphatidic acid activates NF-kappaB in fibroblasts. A requirement for multiple inputs.
AuthorsShahrestanifar M, Fan X, Manning DR
JournalJ Biol Chem
PubMed ID9920937
Lysophosphatidic acid (LPA) is a growth factor that exerts a number of well characterized biological actions on fibroblasts and other cells. In the present study, we investigated the possibility that LPA activates the transcription factor NF-kappaB. NF-kappaB is a target of cytokines, but its activation by other classes of agonists ... More
Nuclear diacylglycerol produced by phosphoinositide-specific phospholipase C is responsible for nuclear translocation of protein kinase C-alpha.
AuthorsNeri LM, Borgatti P, Capitani S, Martelli AM
JournalJ Biol Chem
PubMed ID9792687
It is well established that an independent inositide cycle is present within the nucleus, where it is involved in the control of cell proliferation and differentiation. Previous results have shown that when Swiss 3T3 cells are treated with insulin-like growth factor-I (IGF-I) a rapid and sustained increase in mass of ... More
The regulation of superoxide generation and nitric oxide synthesis by C-reactive protein.
AuthorsRatnam S, Mookerjea S
JournalImmunology
PubMed ID9767445
Activated macrophages utilize both reactive oxygen intermediates and reactive oxynitrogen intermediates for defence against microbes. However, simultaneous generation of superoxide (O- 2;) and nitric oxide (NO) could be harmful to host cells due to the production of peroxynitrite, nitrogen dioxide and hydroxyl radicals. Therefore, the regulation of the production of ... More
Protein kinase C eta mediates lipopolysaccharide-induced nitric-oxide synthase expression in primary astrocytes.
AuthorsChen CC, Wang JK, Chen WC, Lin SB
JournalJ Biol Chem
PubMed ID9677361
The signaling pathway involved in protein kinase C (PKC) activation and role of PKC isoforms in lipopolysaccharide (LPS)-induced nitric oxide (NO) release were studied in primary cerebellar astrocytes. LPS caused a dose- and time-dependent increase in NO release and inducible NO synthase (iNOS) expression. The tyrosine kinase inhibitor, genestein, the ... More
Agonist-independent, muscle-type-specific signal transduction pathways in cat esophageal and lower esophageal sphincter circular smooth muscle.
AuthorsSohn UD, Han B, Tashjian AH, Behar J, Biancani P
JournalJ Pharmacol Exp Ther
PubMed ID7536246
Smooth muscle cells isolated from the circular muscle layer of cat esophagus and lower esophageal sphincter (LES) exhibit distinct contractile intracellular signal transduction pathways in response to acetylcholine. To determine whether these contractile pathways are muscle type dependent, the authors examined the signal transduction pathways utilized by substance P and ... More
Insulin produces a growth hormone-like increase in intracellular free calcium concentration in okadaic acid-treated adipocytes.
AuthorsGaur S, Schwartz Y, Tai LR, Frick GP, Goodman HM
JournalEndocrinology
PubMed ID9832433
In vivo, GH and insulin usually produce opposing effects on carbohydrate and lipid metabolism in adipocytes, even though their signal transduction pathways overlap. However, when added to rat adipocytes that have been made GH deficient, GH briefly produces responses that are qualitatively like those of insulin. Subsequently, GH induces refractoriness ... More
Ras-dependent and -independent pathways target the mitogen-activated protein kinase network in macrophages.
AuthorsBüscher D, Hipskind RA, Krautwald S, Reimann T, Baccarini M
JournalMol Cell Biol
PubMed ID7799956
Mitogen-activated protein kinases (MAPKs) are activated upon a variety of extracellular stimuli in different cells. In macrophages, colony-stimulating factor 1 (CSF-1) stimulates proliferation, while bacterial lipopolysaccharide (LPS) inhibits cell growth and causes differentiation and activation. Both CSF-1 and LPS rapidly activate the MAPK network and induce the phosphorylation of two ... More
Leukotriene D4-induced contraction of cat esophageal and lower esophageal sphincter circular smooth muscle.
AuthorsKim N, Cao W, Song IS, Kim CY, Sohn UD, Harnett KM, Biancani P
JournalGastroenterology
PubMed ID9753495
BACKGROUND & AIMS: In esophageal circular muscle, acetylcholine activates phosphatidylcholine-specific phospholipases C and D and phospholipase A2, producing diacylglycerol and arachidonic acid, which cause contraction by interacting synergistically to activate protein kinase C. In a model of acute esophagitis, leukotriene D4 (LTD4) contributes to acetylcholine-induced contraction. We examined intracellular signaling ... More
Activation of a mitogen-activated protein kinase (ERK2) by the 5-hydroxytryptamine1A receptor is sensitive not only to inhibitors of phosphatidylinositol 3-kinase, but to an inhibitor of phosphatidylcholine hydrolysis.
AuthorsCowen DS, Sowers RS, Manning DR
JournalJ Biol Chem
PubMed ID8798386
A variety of receptors coupled to GTP-binding regulatory proteins (G proteins) initiate signals that culminate in activation of the mitogen-activated protein kinases ERK1 and ERK2. We demonstrate here that the human 5-HT1A receptor expressed in Chinese hamster ovary cells similarly promotes activation of ERK1 and ERK2, but that the pathway ... More
Ectopic head and foot formation in Hydra: diacylglycerol-induced increase in positional value and assistance of the head in foot formation.
AuthorsMüller WA
JournalDifferentiation
PubMed ID2340970
In wild type Hydra magnipapillata, daily application of the protein kinase C activator diacylglycerol (DAG) evokes sprouting of periodically spaced ectopic heads along the body column and leads to loss of the ability to regenerate proximal structures including the foot. The present transplantation studies show that the appearance of ectopic ... More
Basement membrane biosynthesis as a target for developing inhibitors of angiogenesis with anti-tumor properties.
AuthorsMaragoudakis ME, Missirlis E, Karakiulakis GD, Sarmonica M, Bastakis M, Tsopanoglou N
JournalKidney Int
PubMed ID7679456
Basement membrane (BM) exerts profound influence on endothelial cell (EC) behavior. In addition BM is a structural element of blood vessels; in fact at some point of their formation blood vessels are bare EC tubes lined with the BM produced by these EC. We thought, therefore, that a quantitative relationship ... More