Abstract
Traditionally, venoms are assessed, usually following a standard list of potential activities including hypotensive, hemorrhagic, edema and neurotoxicity. This is then followed by the search of toxins in the venoms which contribute to the observed pathophysiological effect. Typically this is done by isolation of the toxin from the venom via biochemical procedures. Alternatively, toxins are cloned and expressed from cDNA libraries generated from venom gland RNA followed by assessment of biological/biochemical function and ultimately pathophysiological effect on the experimental model. These approaches have provided the field with a rich understanding of the potential role of toxins, but may fall short in terms of fully describing the actual function of the toxin in the context of the whole venom and whole animal. This mode of investigation likely does not provide a full understanding of the complete range of biological activities of the venoms and toxins since the suite of assays conducted are generally limited. One data-rich approach that has recently been exploited for further understanding the biological activities and functional potential of venoms and toxins is the study of their ability to alter gene expression in the host. This chapter will discuss how this approach may be of value in terms of drug discovery based on venom produced alteration of gene expression profiles using Connectivity Maps.
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References
Calvete, J.J., 2009. Antivenomics and venom phenotyping: a marriage of convenience to address the performance and range of clinical use of antivenoms. Toxicon. Dec 29 [Epub ahead of print].
Carrijo-Carvalho, L.C., Chudzinski-Tavassi, A.M., 2007. The venom of the Lonomia caterpillar: an overview. Toxicon 49, 741–757.
Cominetti, M.R., Terruggi, C.H.B., Ramos, O.H.P., Fox, J.W., Mariano-Oliveria A., De Freitas, M.S., Figueiredo, C.C., Morandi, V., Selistre-De-Araujo, H.S., 2004. Alternagin-C, a disintegrin-like protein, induces vascular endothelial cell growth factor (VEGF) expression and endothelial cell proliferation in vitro. J. Biol. Chem. 279, 18247–18255.
da Silveira, R.B., Pigozzo, R.B., Chaim, O.M., Appel, M.H., Dreyfuss, J.L., Toma, L., Mangili, O.C., Gremski, W., Dietrich, C.P., Nader, H.B., Veiga, S.S., 2006. Molecular cloning and functional characterization of two isoforms of dermonecrotic toxin from Loxosceles intermedia (brown spider) venom gland. Biochimie 88, 1241–1253.
De Leon, D.D., Farzad, C., Crutchlow, M.F. Brestelli, J., Tobias, J., Kaestner, K.H., Stoffers, D.A., 2006. Identification of transcriptional targets during pancreatic growth after partial pancreatectomy and exendin-4 treatment. Physiol. Genomics 24, 133–143.
Dragulev, B., Bao, Y., Ramos-Cerrillo, B., Vazquez, H., Olvera, A., Stock, R., Algaron, A., Fox, J.W., 2007. Up-regulation of IL-6, IL-8, CXCL1, and CXCL2 dominates gene expression in human fibroblast cells exposed to Loxosceles reclusa sphingomyelinase D: insights into spider venom dermonecrosis. J. Invest. Dermatol. 127, 1264–1266.
Eng, J., Kleinman, W.A., Singh, L., Singh, G., Raufman, J.P., 1992. Isolation and characterization of exendin-e, an exendin-3 analogue from Heloderma suspectum venom. Further evidence for an exendin receptor o dispersed acini from guinea pig pancreas. J. Biol. Chem. 267, 7402–7405.
Fox, J.W., Serrano, S.M., 2009. Timeline of key events in snake venom metalloproteinase research. J. Proteomics 72, 200–209.
Fox, J.W., Serrano, S.M.T., 2007. Approaching the golden age of natural product pharmaceuticals from venom libraries: an overview of toxins and toxin-derivatives currently involved in therapeutic or diagnostic applications. Curr. Pharm. Design 13, 2977–2934.
Gallagher, P.G., Bao, Y., Serrano, S.M.T., Kamiguti, A.S., Theakston, R.D., Fox, J.W., 2003. Use of microarrays for investigating the subtoxic effects of snake venoms: insights into venom-induced apoptosis in human umbilical vein endothelial cells. Toxicon 41, 429–440.
Gallagher, P.G., Bao, Y., Serrano, S.M.T., Laing, G.D., Theakston, R.D.G., Gutierrez, J.M., Escalante, T., Moura-da-Silva, A.M., Nischt, R., Mauch, C., Moskaluk, C., Fox, J.W., 2005. Role of the snake venom toxin jararhagin in proinflammatory pathogenesis: in vitro and in vivo gene expression analysis of the effects of the toxin. Arch. Biochem. Biophys. 441, 1–15.
Ghanaat-Pour, H., Sjoholm, A., 2009. Gene expression regulated by pioglitazone and exenatide in normal and diabetic rat islets exposed to lipotoxicity. Diabetes/Metab Res. Rev. 25, 163–184.
Gutierrez, J.M., Rucavado, A., Escalante, T., Lomonte, B., Angulo, Y., Fox, J.W. 2009. Tissue pathology induced by snake venoms: how to understand a complex pattern of alterations from a systems biology perspective. Toxicon 55, 166–170.
Jang, H.-S., Chung, H.-S., Ko, E., Shin, J.S., Shin, M.K., Hong, M.C., Kim, Y., Min, B.I., Bae, H., 2009. Microarray analysis of gene expression profiles in response to treatment with bee venom in lipopolysaccharide active RAW 264.7 cells. J. Ethnopharm. 121, 213–220.
Kini, R.M., 2006. Anticoagulant proteins from snake venoms: structure, function and mechanism. Biochem. J. 397, 377–387.
Lamb, J. Crawford, E.D., Peck, D., Modell, J.W., Blat, I.C., Wrobel, M.J., Lerner, J., Brunet, J.P., Subramanian, A., Ross, K.N., Reich, M., Hieronymus, H., Wei, G., Armstrong, S.A., Haggarty, S.J., Clemons, P.A., Wei, R., Carr, S.A., Lander, E.S., Golub, T.R., 2006. The Connectivity Map: using gene-expression signatures to connect small molecules, genes and disease. Science 313, 1929–1935.
Pachiappan, A., Thwin, M.M., Manikandan, J., Gopalakrishnakone, P., 2005. Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom: global gene expression analysis using microarray. Toxicon 46, 883–899.
Pahari, S., Mackessy, S.P., Kini, R.M. 2007. The venom gland transcriptome of the Desert Massasauga rattlesnake (Sistrusus catenatus edwardsii) towards an understanding of venom composition among advanced snakes (Superfamily Colubroidea). BMC Mol. Biol. 8, 115–121.
Pinto, A.F., Dragulev, B., Guimaraes, J.A., Fox, J.W., 2008. Novel perspectives on the pathogenesis of Lonomia oblique caterpillar envenomation based on assessment of host response by gene expression analysis. Toxicon 51, 1119–1128.
Swanson, D.L., Vetter, R.S., 2006. Loxoscelism. Clin. Dermatol. 24, 213–221.
Yin, C.S., Lee, H.J., Hong, S.J., Chung, J.H., Koh, H.G., 2005. Microarray analysis of gene expression in chondrosarcoma cells treated with bee venom. Toxicon 45, 81–91.
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Fox, J.W. (2010). Insights in to Venom and Toxin Activities and Pharmacological/Therapeutic Potential Using Gene Expression Profiling. In: Kini, R., Clemetson, K., Markland, F., McLane, M., Morita, T. (eds) Toxins and Hemostasis. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9295-3_5
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DOI: https://doi.org/10.1007/978-90-481-9295-3_5
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