Phosphoinositide and phospholipid phosphorylation and hydrolysis pathways
—Organophosphate and organochlorine pesticides effects

DOI: 10.4236/abc.2013.33A004   PDF   HTML   XML   4,068 Downloads   6,628 Views   Citations


Phospholipid and phosphoinositide phosphorylation pathways have been shown to be of crucial importance on producing lipid mediators. The earlier findings reported on lipid molecules playing roles in different metabolic pathways used to assign them the exclusive role of second messenger generators. Several researchers have recently described how direct interaction of phospholipids and phosphoinositides with molecules or organelles, without the need for producing second messenger molecules, is responsible for their mechanism of action. Organophosphate and organochlorine pesticide toxicity mechanisms have been extensively studied in relation to their well known effects on cholinesterase activities and on the alterations of electric activity in the nervous system of different organisms respectively. There is little but consistent evidence that some compounds, including in both groups of pesticides, are also able to interact with phospholipid and phosphoinositide phosphorylation pathways in several organisms and tissues. The present review consists of an actualization of basic research on phospholipid and phosphoinositide phosphorylation and hydrolysis pathways, as well as a description of some reported evidences for the effects of the above mentioned pesticides on them.

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Fonovich, T. and Magnarelli, G. (2013) Phosphoinositide and phospholipid phosphorylation and hydrolysis pathways
—Organophosphate and organochlorine pesticides effects
. Advances in Biological Chemistry, 3, 22-35. doi: 10.4236/abc.2013.33A004.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Koch, M. and Holt, M. (2012) Coupling exo- and endo-cytosis: An essential role for PIP2 at the synapse. Biochim Biophys Acta, 1821, 1114-1132.
[2] Krahn, M.P. and Wodarz, A. (2012) Phosphoinositide lipids and cell polarity: Linking the plasma membrane to the cytocortex. Essays in Biochemistry, 53, 15-27. doi:10.1042/bse0530015
[3] Delage, E., Puyaubert, J., Zachowski, A. and Ruelland, E. (2013) Signal transduction pathways involving phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5bisphosphate: Convergences and divergences among eukaryotic kingdoms. Progress in Lipid Research, 52, 1-14. doi:10.1016/j.plipres.2012.08.003
[4] Kim, Y.J., Jahan, N. and Bahk, Y.Y. (2013) Biochemistry and structure of phosphoinositide phosphatases. BMB Reports, 46, 1-8. doi:10.5483/BMBRep.2013.46.1.261
[5] Stephens, L., Mc Gregor, A. and Hawkins, P. (2000) Phosphoinositide3-kinases, regulation by cell surface receptors and function of 3-phosphorylated phospholipids in “Biology of Phosphoinositides”. Oxford University Press, Oxford, 32-108.
[6] Mayinger, P. (2012) Phosphoinositides and vesicular membrane traffic. Biochim Biophys Acta, 1821, 1104-1113. doi:10.1016/j.bbalip.2012.01.002
[7] Shenker, B.J., Ali, H., Boesze-Battaglia, K. (2011) PIP3 regulation as promising targeted therapy of mast-cellmediated diseases. Current Pharmaceutical Design, 17, 3815-3822. doi:10.2174/138161211798357926
[8] Dippold, H.C., Ng, M.M., Farber-Katz, S.E., Lee, S.K., Kerr, M.L., Peterman, M.C., Sim, R., Wiharto, P.A., Galbraith, K.A., Madhavarapu, S., Fuchs, G.J., Meerloo, T., Farquhar, M.G., Zhou, H. and Field, S.J. (2009) GOLPH3 bridges phosphatidylinositol-4-phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell, 139, 337-351. doi:10.1016/j.cell.2009.07.052
[9] Millarte, V. and Farhan, H. (2012) The Golgi in cell migration: Regulation by signal transduction and its implications for cancer cell metastasis. Scientific World Journal, 2012, 498278. doi:10.1100/2012/498278
[10] Piao, H. and Mayinger, P. (2012) Growth and metabolic control of lipid signalling at the Golgi. Biochemical Society Transactions, 40, 205-209. doi:10.1042/BST20110637
[11] Kremmyda, L.S., Tvrzicka, E., Stankova, B. and Zak, A. (2011) Fatty acids as biocompounds: Their role in human metabolism, health and disease: a review. part 2: Fatty acid physiological roles and applications in human health and disease. Biomedical Papers, 155, 195-218. doi:10.5507/bp.2011.052
[12] Viiri, K., Mäki, M. and Lohi, O. (2012) Phosphoinositides as regulators of protein-chromatin interactions. Science Signaling, 5, e19. doi:10.1126/scisignal.2002917
[13] Barlow, C.A., Laishram, R.S. and Anderson, R.A. (2010). Nuclear phosphoinositides: A signaling enigma wrapped in a compartmental conundrum. Trends in Cell Biology, 20, 25-35.
[14] Irvine, R.F. (2006) Nuclear inositide signalling—Expansion, structures and clarification. Biochimica et Biophysica Acta, 1761, 505-508.
[15] Slotte, P.J. (2013) Molecular properties of various structurally defined sphingomyelins—Correlation of structure with function. Progress in Lipid Research, 52, 2, 206219. doi:10.1016/j.plipres.2012.12.001
[16] Bieberich, E. (2012) It’s a lipid’s world: Bioactive lipid metabolism and signaling in neural stem cell differentiation. Neurochemical Research, 37, 1208-1229. doi:10.1007/s11064-011-0698-5
[17] Souza, M.S., Magnarelli de Potas, G. and Pechén de D’ Angelo, A.M. (2004) Organophosphorous and organochlorine pesticides affect human placental phosphoinositides metabolism and PI-4 kinase activity. Journal of Biochemical and Molecular Toxicology, 18, 30-36. doi:10.1002/jbt.20003
[18] Downes, C.P. and Macphee, C.H. (1990) Myo-inositol metabolites as cellular signals. European Journal of Biochemistry, 193, 1-18. doi:10.1111/j.1432-1033.1990.tb19297.x
[19] Catt, K.J., Hunyady, L. and Balla, T. (1991) Second messengers derived from inositol lipids. Journal of Bioenergetics and Biomembranes, 23, 7-27.
[20] Tse, A. and Tse, F.W. (1998) α-adrenergic stimulation of cytosolic Ca2+ oscillations and exocytosis in identified rat corticotrophs. Journal of Physiology, 512, 385-393. doi:10.1111/j.1469-7793.1998.385be.x
[21] Kim, M.H., Choi, B.H., Jung, S.R., Sernka, T.J., Kim, S., Kim, K.T., Hille, B., Nguyen, T.D. and Koh, D.S. (2008) Protease-activated receptor-2 increases exocytosis via multiple signal transduction pathways in pancreatic duct epithelial cells. Journal of Biological Chemistry, 283, 18711-18720. doi:10.1074/jbc.M801655200
[22] Zaika, O., Zhang, J. and Shapiro, M.S. (2011) Combined phosphoinositide and Ca2+ signals mediating receptor specificity toward neuronal Ca2+ channels. Journal of Biological Chemistry, 286, 830-841. doi:10.1074/jbc.M110.166033
[23] Bohdanowicz, M., Cosío, G., Backer, J.M. and Grinstein, S. (2010) Class I and class III phosphoinositide 3-kinases are required for actin polymerization that propels phagosomes. Journal of Cell Biology, 191, 999-1012.
[24] Bohdanowicz, M. and Grinstein, S. (2013) Role of phospholipids in endocytosis, phagocytosis, and macropinocytosis. Physiological Reviews, 93, 69-106.
[25] Wen, P.J., Osborne, S.L. and Meunier, F.A. (2012) Phosphoinositides in neuroexocytosis and neuronal diseases. Current Topics in Microbiology and Immunology, 362, 87-98.
[26] Trebak, M., Lemonnier, L., DeHaven, W.I., Wedel, B.J., Bird, G.S. and Putney Jr., J.W. (2009) Complex functions of phosphatidylinositol 4,5-bisphosphate in regulation of TRPC5 cation channels. European Journal of Physiology, 457, 757-769. doi:10.1007/s00424-008-0550-1
[27] Criswell, K.A., Loch-Caruso, R. and Stuenkel, E.L. (1995) Lindane inhibition of gap junctional communication in myometrial myocytes is partially dependent on phosphoinositide-generated second messengers. Toxicology and Applied Pharmacology, 130, 280-293. doi:10.1006/taap.1995.1033
[28] Balduini, W., Cimino, M., Renò, F., Marini, P., Princivalle, A. and Cattabeni, F. (1993) Effects of postnatal or adult chronic acetylcholinesterase inhibition on muscarinic receptors, phosphoinositide turnover and m1 mRNA expression. European Journal of Pharmacology, 248, 281-288.
[29] Sun, X., Liu, X.B., Martinez, J.R. and Zhang, G.H. (2000) Effects of low concentrations of paraoxon on Ca2+ mobilization in a human parotid salivary cell-line HSY. Archives of Oral Biology, 45, 621-638. doi:10.1016/S0003-9969(00)00043-1
[30] Zhang, H., Liu, J. and Pope, C.N. (2002) Age-related effects of chlorpyrifos on muscarinic receptor-mediated signaling in rat cortex. Archives of Toxicology, 75, 676-684. doi:10.1007/s00204-001-0309-3
[31] Suh, P.G., Park, J.I., Manzoli, L., Cocco, L., Peak, J.C., Katan, M., Fukami, K., Kataoka, T., Yun, S. and Ryu, S.H. (2008) Multiple roles of phosphoinositide-specific phospholipase C isozymes. BMB Report, 41, 415-434. doi:10.5483/BMBRep.2008.41.6.415
[32] Drin, G. and Scarlata, S. (2007) Stimulation of phospholipase Cbeta by membrane interactions, interdomain movement, and G protein binding—How many ways can you activate an enzyme? Cell Signal, 19, 1383-1392. doi:10.1016/j.cellsig.2007.04.006
[33] Suzuki, K., Saito, S.Y. and Ishikawa, T. (2012) Involvement of phosphatidylcholine-specific phospholipase C in thromboxane A2 receptor-mediated extracellular Ca2+ influx in rat aorta. European Journal of Pharmacology, 677, 123-130. doi:10.1016/j.ejphar.2011.12.005
[34] Strielkov, I.V., Kizub, I.V., Khromov, A.S. and Soloviev, A.I. (2013) Evidence for the role of phosphatidylcholinespecific phospholipase C in sustained hypoxic pulmonary vasoconstriction. Vascular Pharmacology, 58, 292-298. doi:10.1016/j.vph.2013.02.002
[35] Xia, L., Zhang, D., Wang, C., Wei, F. and Hu, Y. (2012). PC-PLC is involved in osteoclastogenesis induced by TNF-α through upregulating IP3R1 expression. FEBS Letters, 586, 3341-3348. doi:10.1016/j.febslet.2012.07.015
[36] Ernsberger, P., Friedman, J.E. and Koletsky, R.J. (1997) The I1-imidazoline receptor: From binding site to therapeutic target in cardiovascular disease. Journal of hypertension. Supplement, 15, S9-S23. doi:10.1097/00004872-199715011-00002
[37] Li, H., Zhang, L., Yin, D., Zhang, Y. and Miao, J. (2010) Targeting phosphatidylcholine-specific phospholipase C for atherogenesis therapy. Trends in Cardiovascular Medicine, 20, 172-176. doi:10.1016/j.tcm.2011.02.002
[38] Shao, J., Sun, C., Su, L., Zhao, J., Zhang, S. and Miao, J. (2012) Phosphatidylcholine-specific phospholipase C/ heat shock protein 70 (Hsp70)/transcription factor B-cell translocation gene 2 signaling in rat bone marrow stromal cell differentiation to cholinergic neuron-like cells. The International Journal of Biochemistry & Cell Biology, 44, 2253-2260. doi:10.1016/j.biocel.2012.09.013
[39] Abalsamo, L., Spadaro, F., Bozzuto, G., Paris, L., Cecchetti, S., Lugini, L., Iorio, E., Molinari, A., Ramoni, C. and Podo, F. (2012) Inhibition of phosphatidylcholinespecific phospholipase C results in loss of mesenchymal traits in metastatic breast cancer cells. Breast Cancer Research, 14, R50. doi:10.1186/bcr3151
[40] Moya de Juri, M.G., Magnarelli De Potas, G. and Pechen de D’Angelo, A.M. (2002) Alteration of thrombine-signaling mechanism by heptachlor in human platelets. Journal of Biochemical and Molecular Toxicology, 16, 189196. doi:10.1002/jbt.10037
[41] Lu, C.H, Lee, K.C., Chen, Y.C., Cheng, J.S., Yu, M.S., Chen, W.C. and Jan, C.R. (2000) Lindane (gamma-hexachlorocyclohexane) induces internal Ca2+ release and capacitative Ca2+ entry in Madin-Darby canine kidney cells. Pharmacology Toxicology, 87, 149-155. doi:10.1034/j.1600-0773.2000.d01-65.x
[42] Hansen, M.E. and Matsumura, F. (2001) Effects of heptachlor epoxide on components of various signal transduction pathways important in tumor promotion in mouse hepatoma cells. Determination of the most sensitive tumor promoter related effect induced by heptachlor epoxide. Toxicology, 160, 139-153. doi:10.1016/S0300-483X(00)00445-5
[43] Katz, L.S. and Marquis, J.K. (1992) Organophosphateinduced alterations in muscarinic receptor binding and phosphoinositide hydrolysis in the human SK-N-SH cell line. Neurotoxicology, 13, 365-78.
[44] Magnarelli de Potás, G.M. and Pechén de D’Angelo, A.M. (1993) Phosphoinositide phosphorylation and shape changes produced by phosmet-oxon in human erythrocytes. Comparative Biochemistry and Physiology Part C, 106, 561-566.
[45] Pascual, F. and Carman, G.M. (2013) Phosphatidate phosphatase, a key regulator of lipid homeostasis. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids, 1831, 514-522. doi:10.1016/j.bbalip.2012.08.006
[46] Dwyer, J.R., Donkor, J., Zhang, P., Csaki, L.S., Vergnes, L., Lee, J.M., Dewald, J., Brindley, D.N., Atti, E., Tetradis, S., Yoshinaga, Y., De Jong, P.J., Fong, L.G., Young, S.G. and Reue, K. (2012) Mouse lipin-1 and lipin-2 cooperate to maintain glycerolipid homeostasis in liver and aging cerebellum. Proceedings of the National Academy of Sciences of the United States of America, 109, E2486E2495. doi:10.1073/pnas.1205221109
[47] Siniossoglou, S. (2013) Phospholipid metabolism and nuclear function: Roles of the lipin family of phosphatidic acid phosphatases. Biochimica et Biophysica Acta (BBA)Molecular and Cell Biology of Lipids, 1831, 575-581. doi:10.1016/j.bbalip.2012.09.014
[48] Valdearcos, M., Esquinas, E., Meana, C., Gil-de-Gómez, L., Guijas, C., Balsinde, J. and Balboa, M. A. (2011) Subcellular localization and role of lipin-1 in human macrophages. Journal of Immunology, 186, 6004-6013. doi:10.4049/jimmunol.1003279
[49] Domart, M.C., Hobday, T.M., Peddie, C.J., Chung, G.H., Wang, A., Yeh, K., Jethwa, N., Zhang, Q., Wakelam, M.J., Woscholski, R., Byrne, R.D., Collinson, L.M., Poccia, D.L. and Larijani, B. (2012) Acute manipulation of diacylglycerol reveals roles in nuclear envelope assembly & endoplasmic reticulum morphology. PLoS One, 7, e51150. doi:10.1371/journal.pone.0051150
[50] Mall, M., Walter, T., Gorjánácz, M., Davidson, I.F., Nga Ly-Hartig, T.B., Ellenberg, J. and Mattaj, I.W. (2012) Mitotic lamin disassembly is triggered by lipid-mediated signaling. The Journal of Cell Biology, 198, 981-990. doi:10.1083/jcb.201205103
[51] Kunkel, M.T. and Newton, A.C. (2010) Calcium transduces plasma membrane receptor signals to produce diacylglycerol at Golgi membranes. The Journal of Biological Chemistry, 285, 22748-22752. doi:10.1074/jbc.C110.123133
[52] Bomser, J.A., Quistad, G.B. and Casida, J.E. (2002) Chlorpyrifos oxon potentiates diacylglycerol-induced extracellular signal-regulated kinase (ERK 44/42) activation, possibly by diacylglycerol lipase inhibition. Toxicology and Applied Pharmacology, 178, 29-36. doi:10.1006/taap.2001.9324
[53] Ramos, I., Cisint, S.B., Crespo, C.A., Medina, M.F. and Fernández, S.N. (2009) Subcellular localization of calcium and Ca-ATPase activity during nuclear maturation in Bufo arenarum oocytes. Zygote, 17, 253-260. doi:10.1017/S0967199409005334
[54] Stith, B.J., Goalstone, M., Silva, S. and Jaynes, C. (1993) Inositol 1,4,5-trisphosphate mass changes from fertilization through first cleavage in Xenopus laevis. Molecular Biology of the Cell, 4, 435-443.
[55] Ciapa, B., Borg, B. and Whitaker, M. (1992) Polyphospho-inositide metabolism during the fertilization wave in sea urchin eggs. Development, 115, 187-195.
[56] Santella, L., Lim, D. and Moccia, F. (2004) Calcium and fertilization: The beginning of life. Trends in Biochemical Sciences, 29, 400-408. doi:10.1016/j.tibs.2004.06.009
[57] Shearer, J., De Nadai, C., Emily-Fenouil, F., Gache, C., Whitaker, M. and Ciapa, B. (1999) Role of phospholipase Cgamma at fertilization and during mitosis in sea urchin eggs and embryos. Development, 126, 2273-2284.
[58] Runft, L.L., Carroll, D.J., Gillett, J., Giusti, A.F., O’Neill, F.J. and Foltz, K.R. (2004) Identification of a starfish egg PLC-gamma that regulates Ca2+ release at fertilization. Developmental Biology, 269, 220-236. doi:10.1016/j.ydbio.2004.01.031
[59] Yin, X. and Eckberg, W.R. (2009) Characterization of phosphor-lipases C beta and gamma and their possible roles in Chaetopterus egg activation. Molecular Reproduction and Development, 76, 460-470. doi:10.1002/mrd.20961
[60] Tokmakov, A.A., Sato, K.I., Iwasaki, T. and Fukami, Y. (2002) Src kinase induces calcium release in Xenopus egg extracts via PLCgamma and IP3-dependent mechanism. Cell Calcium, 32, 11-20. doi:10.1016/S0143-4160(02)00078-7
[61] Halet, G., Tunwell, R., Balla, T., Swann, K. and Carroll, J. (2002) The dynamics of plasma membrane PtdIns(4,5)P2 at fertilization of mouse eggs. Journal of Cell Science, 115, 2139-2149.
[62] Ito, J., Yoon, S.Y., Lee, B., Vanderheyden, V., Vermassen, E., Wojcikiewicz, R., Alfandari, D., De Smedt, H., Parys, J.B. and Fissore, R.A. (2008.) Inositol 1,4,5-trisphosphate receptor 1, a widespread Ca2+ channel, is a novel substrate of polo-like kinase 1 in eggs. Developmental Biology, 320, 402-413. doi:10.1016/j.ydbio.2008.05.548
[63] Wakai, T., Vanderheyden, V., Yoon, S.Y., Cheon, B., Zhang, N., Parys, J.B. and Fissore, R.A. (2012) Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation. Journal of Cellular Physiology, 227, 705-717. doi:10.1002/jcp.22778
[64] Lee, B., Vermassen, E., Yoon, S.Y., Vanderheyden, V., Ito, J., Alfandari, D., De Smedt, H., Parys, J.B. and Fissore R.A. (2006) Phosphorylation of IP3R1 and the regulation of [Ca2+]i responses at fertilization: A role for the MAP kinase pathway. Development, 133, 4355-4365. doi:10.1242/dev.02624
[65] Igarashi, H., Knott, J.G., Schultz, R.M. and Williams, C.J. (2007) Alterations of PLCbeta1 in mouse eggs change calcium oscillatory behavior following fertilization. Developmental Biology, 312, 321-330. doi:10.1016/j.ydbio.2007.09.028
[66] Kashir, J., Heindryckx, B., Jones, C., De Sutter, P., Parrington, J. and Coward, K. (2010) Oocyte activation, phospholipase C zeta and human infertility. Human Reproduction Update, 16, 690-703. doi:10.1093/humupd/dmq018
[67] Chun, J.T., Puppo, A., Vasilev, F., Gragnaniello, G., Garante, E. and Santella, L. (2010) The biphasic increase of PIP2 in the fertilized eggs of starfish: New roles in actin polymerization and Ca2+ signaling. PLoS One, 5, e14100. doi:10.1371/journal.pone.0014100
[68] Stith, B.J., Woronoff, K., Espinoza, R. and Smart, T. (1997) Sn-1,2-diacylglycerol and choline increase after fertilization in Xenopus laevis. Molecular Biology of the Cell, 8, 755-765.
[69] Morrill, G.A. and Kostellow, A.B. (1999) Progesterone induces meiotic division in the amphibian oocyte by releasing lipid second messengers from the plasma membrane. Steroids, 64, 157-167. doi:10.1016/S0039-128X(98)00093-2
[70] Fonovich de Schroeder, T.M. and Pechén de D’Angelo, A.M. (1991) Dieldrin effects on phospholipid and phosphoinositide metabolism in Bufo arenarum oocytes. Comparative Biochemistry and Physiology Part C: Comparative Pharmacology, 98, 287-292. doi:10.1016/0742-8413(91)90207-A
[71] Fonovich de Schroeder, T.M. and Pechén de D’Angelo, A.M. (1995a) Dieldrin modifies the hydrolysis of PIP2 and decreases the fertilization rate in Bufo arenarum oocytes. Comparative Biochemistry and Physiology-Part C, 112, 61-67.
[72] Fonovich de Schroeder, T.M. and Pechén de D’Angelo, A.M. (1995b) The effect of dieldrin on Clostridium perfringens phosphatidylcholine phospholipase C activity. Pesticide Biochemistry and Physiology, 51, 170-177. doi:10.1006/pest.1995.1017

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