Browse > Article

D609, an Inhibitor of Phosphatidylcholine-specific Phospholipase C, Inhibits Group IV Cytosolic Phospholipase A2  

Kang, Mi Sun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Jung, Sung Yun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Jung, Kwang Mook (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Kim, Seok Kyun (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Ahn, Kyong Hoon (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Kim, Dae Kyong (Department of Environmental and Health Chemistry, College of Pharmacy, Chung-Ang University)
Publication Information
Molecules and Cells / v.26, no.5, 2008 , pp. 481-485 More about this Journal
Abstract
As an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), D609 has been widely used to explain the role of PC-PLC in various signal transduction pathways. This study shows that D609 inhibits group IV cytosolic phospholipase $A_2$ ($cPLA_2$), but neither secretory $PLA_2$ nor a $Ca^{2+}$-dependent $PLA_2$. Dixon plot analysis shows a mixed pattern of noncompetitive and uncompetitive inhibition with $K_i=86.25{\mu}M$ for the $cPLA_2$ purified from bovine spleen. D609 also time- and dose-dependently reduces the release of arachidonic acid from a $Ca^{2+}$- ionophore A23187-stimulated MDCK cells. In the AA release experiment, $IC_{50}$ of D609 was ${\sim375}{\mu}M$, suggesting that this reagent may not enter the cells easily. The present study indicates that the inhibitory effects of D609 on various cellular responses may be partially attributable to the inhibition of $cPLA_2$.
Keywords
AA release; $cPLA_2$; D609; DAG; MDCK cells; PC-PLC;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
1 Andrei, C., Margiocco, P., Poggi, A., Lotti, L.V., Torrisi, M.R., and Rubartelli, A. (2004). Phospholipases C and A2 control lysosome- mediated IL-1 beta secretion: Implications for inflammatory processes. Proc. Natl. Acad. Sci. USA 101, 9745-9750
2 Bradford, M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254   DOI   ScienceOn
3 Cai, H., Erhardt, P., Szeberenyi, J., Diaz-Meco, M.T., Johansen, T., Moscat, J., and Cooper, G.M. (1992). Hydrolysis of phosphatidylcholine is stimulated by Ras proteins during mitogenic signal transduction. Mol. Cell. Biol. 12, 5329-5335   DOI
4 Cheng, J., Weber, J.D., Baldassare, J.J., and Raben, D.M., (1997). Ablation of Go alpha-subunit results in a transformed phenotype and constitutively active phosphatidylcholine-specific phospholipase C. J. Biol. Chem. 272, 17312-17319   DOI   ScienceOn
5 Dieter, P., Kolada, A., Kamionka, S., Schadow, A., and Kaszkin, M. (2002). Lipopolysaccharide-induced release of arachidonic acid and prostaglandins in liver macrophages: regulation by Group IV cytosolic phospholipase $A_2$, but not by Group V and Group IIA secretory phospholipase $A_2$. Cell. Signal. 14, 199-204   DOI   ScienceOn
6 Johansen, T., Bjorkoy, G., Overvatn, A., Diaz-Meco, M.T., Traavik, T., and Moscat, J. (1994). NIH 3T3 cells stably transfected with the gene encoding phosphatidylcholine hydrolyzing phospholipase C from Bacillus cereus acquire a transformed phenotype. Mol. Cell. Biol. 14, 646-654   DOI
7 Kennedy, C.R., Hebert, R.L., Do, M.T., and Proulx, P.R. (1997). Bradykinin-stimulated arachidonic acid release from MDCK cells is not protein kinase C dependent. Am. J. Physiol. 273, C1605-1612   DOI
8 O'Flaherty, J.T., Chadwell, B.A., Kearns, M.W., Sergeant, S., and Daniel, L.W. (2001). Protein kinases C translocation responses to low concentrations of arachidonic acid. J. Biol. Chem. 276, 24743-24750   DOI   ScienceOn
9 Pastorino, J.G., Simbula, G., Yamamoto, K., Glascott, P.A., Rothman, R.J., and Farber, J.L. (1996). The cytotoxicity of tumor necrosis factor depends on induction of the mitochondrial permeability transition. J. Biol. Chem. 271, 29792-29798   DOI   ScienceOn
10 Ross, B.M., Kim, D.K., Bonventre, J.V., and Kish, S.J. (1995). Characterization of a novel phospholipase $A_2$ activity in human brain. J. Neurochem. 64, 2213-2221   DOI   ScienceOn
11 Tschaikowsky, K., Schmidt, J., and Meisner, M., (1998). Modulation of mouse endotoxin shock by inhibition of phosphatidylcholinespecific phospholipase C. J. Pharmacol. Exp. Ther. 285, 800-804
12 Wiegmann, K., Schutze, S., Machleidt, T., Witte, D., and Kronke, M., (1994). Functional dichotomy of neutral and acidic sphingomyelinases in tumor necrosis factor signaling. Cell 78, 1005-1015   DOI   ScienceOn
13 Zhang, F., Zhao, G., and Dong, Z. (2001). Phosphatidylcholinespecific phospholipase C regulates activation of RAW264.7 macrophage-like cells by lipopeptide JBT3002. J. Leukoc. Biol. 69, 1060-1066
14 Pettitt, T.R., Martin, A., Horton, T., Liossis, C., Lord, J.M., and Wakelam, M.J. (1997). Diacylglycerol and phosphatidate generated by phospholipases C and D, respectively, have distinct fatty acid compositions and functions. Phospholipase D-derived diacylglycerol does not activate protein kinase C in porcine aortic endothelial cells. J. Biol. Chem. 272, 17354-17359   DOI   ScienceOn
15 Amtmann, E. (1996). The antiviral, antitumoural xanthate D609 is a competitive inhibitor of phosphatidylcholine-specific phospholipase C. Drugs. Exp. Clin. Res. 22, 287-294
16 Xu, J., Weng, Y.I., Simonyi, A., Krugh, B.W., Liao, Z., Weisman, G.A., and Sun, G.Y. (2002). Role of PKC and MAPK in cytosolic $PLA_2$ phosphorylation and arachadonic acid release in primary murine astrocytes. J. Neurochem. 83, 259-270   DOI   ScienceOn
17 Kennedy, C.R., Proulx, P.R., and Hebert, R.L. (1996). Role of $PLA_2$,PLC, and PLD in bradykinin-induced release of arachidonic acid in MDCK cells. Am. J. Physiol. 271, C1064-C1072   DOI
18 Machleidt, T., Kramer, B., Adam, D., Neumann, B., Schutze, S., Wiegmann, K., and Kronke, M. (1996). Function of the p55 tumor necrosis factor receptor "death domain" mediated by phosphatidylcholine- specific phospholipase C. J. Exp. Med. 184, 725-733   DOI
19 Kim, D.K., Suh, P.G., and Ryu, S.H. (1991). Purification and some properties of a phospholipase $A_2$ from bovine platelets. Biochem. Biophys. Res. Commun. 174, 189-196   DOI   ScienceOn
20 Macrez-Lepretre, N., Morel, J.L., and Mironneau, J. (1996). Effects of phospholipase C inhibitors on $Ca^{2+}$ channel stimulation and $Ca^{2+}$ release from intracellular stores evoked by alpha 1A- and alpha 2A-adrenoceptors in rat portal vein myocytes. Biochem. Biophys. Res. Commun. 218, 30-34   DOI   ScienceOn
21 Woo, C.H., Eom, Y.W., Yoo, M.H., You, H.J., Han, H.J., Song, W.K., Yoo, Y.J., Chun, J.S., and Kim, J.H. (2000). Tumor necrosis factor- alpha generates reactive oxygen species via a cytosolic phospholipase $A_2$-linked cascade, J. Biol. Chem. 275, 32357-32362   DOI   ScienceOn
22 Ramoni, C., Spadaro, F., Barletta, B., Dupuis, M.L., and Podo, F. (2004). Phosphatidylcholine-specific phospholipase C in mitogen-stimulated fibroblasts. Exp. Cell. Res. 299, 370-82   DOI   ScienceOn
23 Li, Y., Maher, P., and Schubert, D. (1998). Phosphatidylcholinespecific phospholipase C regulates glutamate-induced nerve cell death. Proc. Natl. Acad. Sci. USA 95, 7748-7753
24 Cuschieri, J., Billgren, J., and Maier, R.V. (2006). Phosphatidylcholine- specific phospholipase C (PC-PLC) is required for LPSmediated macrophage activation through CD14. J. Leukoc. Biol. 80, 407-414   DOI   ScienceOn
25 Cai, H., Erhardt, P., Troppmair, J., Diaz-Meco, M.T., Sithanandam, G., Rapp, U.R., Moscat, J., and Cooper, G.M. (1993). Hydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction. Mol. Cell. Biol. 13, 7645-7651   DOI
26 Monick, M.M., Carter, A.B., Gudmundsson, G., Mallampalli, R., Powers, L.S., and Hunninghake, G.W. (1999). A phosphatidylcholine-specific phospholipase C regulates activation of p42/44 mitogen-activated protein kinases in lipopolysaccharide-stimulated human alveolar macrophages. J. Immunol. 162, 3005-3012
27 Exton, J.H. (1994). Phosphatidylcholine breakdown and signal transduction. Biochim. Biophys. Acta 1212, 26-42   DOI   ScienceOn
28 Zhao, S., Du, X.Y., Chai, M.Q., Chen, J.S., Zhou, Y.C., and Song, J.G. (2002). Secretory phospholipase $A_2$ induces apoptosis via a mechanism involving ceramide generation. Biochim. Biophys. Acta 1581, 75-88   DOI   ScienceOn
29 You, H.J., Seo, J.M., Moon, J.Y., Han, S.S., Ko, Y.G., and Kim, J.H. (2007). Leukotriene synthesis in response to $A_2$3187 is inhibited by methyl- beta-cyclodextrin in RBL-2H3 cells. Mol. Cells 23, 57-63
30 Shin, K.J., Chung, C., Hwang, Y.A., Kim, S.H., Han, M.S., Ryu, S.H., and Suh, P.G. (2002). Phospholipase $A_2$-mediated $Ca^{2+}$ influx by 2,2',4,6-tetrachlorobiphenyl in PC12 cells. Toxicol. Appl. Pharmacol. 178, 37-43   DOI   ScienceOn
31 Kim, D.K., and Bonventre, J.V. (1993). Purification of a 100 kDa phospholipase $A_2$ from spleen, lung and kidney: antiserum raised to pig spleen phospholipase $A_2$ recognizes a similar form in bovine lung, kidney and platelets, and immunoprecipitates phospholipase $A_2$ activity. Biochem. J. 294, 261-270   DOI
32 Bonventre, J.V., (1992). Phospholipase $A_2$ and signal transduction. J. Am. Soc. Nephrol. 3, 128-150
33 Pessin, M.S., and Raben, D.M., (1989). Molecular species analysis of 1,2-diglycerides stimulated by alpha-thrombin in cultured fibroblasts. J. Biol. Chem. 264, 8729-8738
34 Zamorano, J., Rivas, M.D., Garcia-Trinidad, A., Qu, C.K., and Keegan, A.D. (2003). Phosphatidylcholine-specific phospholipase C activity is necessary for the activation of STAT6. J. Immunol. 171, 4203-4209   DOI
35 Schutze, S., Potthoff, K., Machleidt, T., Berkovic, D., Wiegmann, K., and Kronke, M. (1992). TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced "acidic" sphingomyelin breakdown. Cell 71, 765-776   DOI   ScienceOn
36 Gijon, M.A., and Leslie, C.C. (1999). Regulation of arachidonic acid release and cytosolic phospholipase $A_2$ activation. J. Leukoc. Biol. 65, 330-336   DOI
37 McGehee, D.S., Aldersberg, M., Liu, K.P., Hsuing, S.C., Heath, M.J.S., and Tamir, H. (1997). Mechanism of extracellular $Ca^{2+}$receptor-stimulated hormone release from sheep thyroid parafollicular cell. J. Physiol. 502, 31-34   DOI
38 Temes, E., Martin-Puig, S., Aragones, J., Jones, D.R., Olmos, G., Merida, I., and Landazuri, M.O. (2004). Role of diacylglycerol induced by hypoxia in the regulation of HIF-1alpha activity. Biochem. Biophys. Res. Commun. 315, 44-50   DOI   ScienceOn
39 Kiss, Z., and Tomono, M. (1995). Compound D609 inhibits phorbol ester-stimulated phospholipase D activity and phospholipase Cmediated phosphatidylethanolamine hydrolysis. Biochim. Biophys. Acta 1259, 105-108   DOI
40 Luberto, C., and Hannun, Y.A. (1998). 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? J. Biol. Chem. 273, 14550-14559   DOI   ScienceOn
41 Nofer, J.R., Junker, R., Seedorf, U., Assmann, G., Zidek, W., and Tepel, M. (2000). D609-phosphatidylcholine-specific phospholipase C inhibitor attenuates thapsigargin-induced sodium influx in human lymphocytes. Cell. Signal. 12, 289-296   DOI   ScienceOn
42 Muller-Decker, K. (1989). Interruption of TPA-induced signals by an antiviral and antitumoral xanthate compound: inhibition of a phospholipase C-type reaction. Biochem. Biophys. Res. Commun. 162, 198-205   DOI   ScienceOn
43 Diaz-Laviada, I., Larrodera, P., Diaz-Meco, M.T., Cornet, M.E., Guddal, P.H., Johansen, T., and Moscat, J. (1990). Evidence for a role of phosphatidylcholine-hydrolysing phospholipase C in the regulation of protein kinase C by ras and src oncogenes. EMBO. J. 9, 3907-3912
44 Favaron, M., Manev, H., Siman, R., Bertolino, M., Szekely, A.M., DeErausquin, G., Guidotti, A., and Costa, E. (1990). Downregulation of protein kinase C protects cerebellar granule neurons in primary culture from glutamate-induced neuronal death. Proc. Natl. Acad. Sci. USA 87, 1983-1987
45 Lin, L.L., Wartmann, M., Lin, A.Y., Knopf, J.L., Seth, A., and Davis, R.J. (1993). $cPLA_2$ is phosphorylated and activated by MAP kinase. Cell 72, 269-278   DOI   ScienceOn