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Chemical Compound Review

Travex     sodium chlorate

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Disease relevance of sodium chlorate

  • Furthermore, BSC40 cells treated with sodium chlorate to produce undersulfated GAGs are more refractory to vaccinia virus infection [1].
  • To investigate the potential regulation of FGF-2 mitogenic activity by heparan sulfate proteoglycans (HSPG), we have treated human breast cancer cells by glycosaminoglycan degrading enzymes or a metabolic inhibitor of proteoglycan sulfation: sodium chlorate [2].
  • Inhibition experiments with heparin and sodium chlorate showed that heparan sulfates are necessary for HPV 16 VLPs to bind to DC but not to LC [3].
  • Platelet derived growth factor demonstrated a growth stimulating effect on B6FS, whereas no effect was evident on HT1080 fibrosarcoma cells. beta-d-Xyloside had no effect on the basal level or the platelet derived growth factor-induced cell proliferation, whereas sodium chlorate severely reduced the basal level of proliferation in both cell lines [4].
  • Undersulfation of glycosaminoglycans induced by sodium chlorate treatment affects the progression of C6 rat glioma, in-vivo [5].

High impact information on sodium chlorate

  • Oncogenic Ras-induced proliferation is abolished by addition of an anti-FGF-2 blocking antibody, suramin, or treatment with either sodium chlorate or heparitinase, demonstrating an autocrine requirement for FGF-2 [6].
  • Treatment of HeLa cells with sodium chlorate, a potent inhibitor of proteoglycan sulfation, reduced luciferase expression by 69% [7].
  • Incubation of cells with sodium chlorate reduced glycosaminoglycan sulfation by > 95% without affecting cell growth [8].
  • Treatment of whole kidneys with sodium chlorate to disrupt proteoglycan synthesis results in the loss of BMP7 expression in the mesenchyme whereas expression in the epithelial components of the kidney are unaffected [9].
  • Addition of alpha2-macroglobulin as well as treatment with heparinase, chondroitinase ABC, and sodium chlorate did not decrease levels of VCAM-1 and E-selectin stimulated by Lp(a), suggesting that neither the low density lipoprotein receptor-related protein nor cell-surface proteoglycans are involved in Lp(a)-induced adhesion molecule production [10].

Chemical compound and disease context of sodium chlorate


Biological context of sodium chlorate

  • Treatment of cells with sodium chlorate, which blocks sulfation of proteoglycans, reduced the binding of aFGF to its low and high affinity binding sites by 95 and 80%, respectively [14].
  • This self-catalyzed cyclization reaction is inhibited by the intercalating dye methidiumpropyl.EDTA (MPE; R.P. Hertzberg and P.B. Dervan (1982) J. Am. Chem. Soc. 104, 313-315) [15].
  • The affinity cleavage reagent methidiumpropyl-EDTA (MPE) [Hertzberg, R. P., & Dervan, P. B. (1982) J. Am. Chem. Soc. 104, 313-315] intercalates between base pairs in helical DNA and, when complexed with Fe(II), cleaves the DNA by oxidative degradation of the deoxyribose [16].
  • Our data showed that both hairpin polyamides preferentially selected DNA sequences having consensus recognition sites as defined by the Dervan pairing rules [17].
  • In contrast, sodium chlorate unexpectedly induced early expression of type II collagen and increased the number of cartilage nodules during chondrogenesis [18].

Anatomical context of sodium chlorate

  • In our studies, Balb/c3T3 fibroblasts were treated with 50 mM sodium chlorate to completely inhibit (99%) sulfation of proteoglycans [19].
  • To test further this hypothesis, the binding capacity of the plasma membrane for the lipase was decreased by inhibiting the sulfation of glycosaminoglycans with sodium chlorate, an inhibitor of sulfate adenyltransferase [20].
  • In the present study, we have demonstrated that treatment of both astrocytic cell lines and primary astrocytes with inhibitors of proteoglycan synthesis, beta-D-xylosides and sodium chlorate, can strongly influence the axon growth promoting properties of both matrix and whole cells [21].
  • Dorsal root ganglia grown on Neu7 cells treated with sodium chlorate extended 2 to 3 times the number of axons for approximately 300 mm longer distance than on control cultures [21].
  • Heparinase digestion of the endothelial cell's glycocalyx or sodium chlorate inhibition of endothelial cell sulfated glycan synthesis significantly reduced the number of adherent H. somnus [22].

Associations of sodium chlorate with other chemical compounds

  • The biological effect of bFGF is conveyed through its binding to the high-affinity receptor sites and the binding is dependent on the presence of cell surface heparin-like molecules, as treatment of cells with heparitinase or sodium chlorate abolishes high-affinity binding and growth inhibition [23].
  • SR-BI-mediated LDL-CE-selective uptake was not inhibited by the proteoglycan synthesis inhibitor, p-nitrophenyl-beta-D-xylopyranoside or by the sulfation inhibitor sodium chlorate, indicating that SR-BI-mediated LDL-CE uptake occurs independently of LDL interaction with cell-surface proteoglycan [24].
  • GGH(Hin139-190) binds sequence specifically to DNA at four 13 base pair sites (termed hixL and secondary) and, in the presence of Ni(OAc)2 and monoperoxyphthalic acid, reacts predominantly at a single deoxyribose position on one strand of each binding site [Mack, D.P., & Dervan, P.B. (1990) J. Am. Chem. Soc. 112, 4604] [25].
  • Testosterone production by dibutryl-cAMP stimulated Leydig cells was also inhibited by sodium chlorate [26].
  • In some experiments, chondrocyte cultures were treated with sodium chlorate (NaClO(3)) to inhibit GAG sulfation, or with chondroitinase ABC (ChABC) to digest chondroitin sulfate (CS) in the matrix [27].

Gene context of sodium chlorate

  • Using a metabolic inhibitor of sulfation, sodium chlorate, we show that the interactions of the CS/DS chains of versican with L- and P-selectin and chemokines are sulfation-dependent but the interaction with CD44 is sulfation-independent [28].
  • In addition, when the sulphation of glycosaminoglycans (GAGs) is prevented by growing the HepG2 cells in the presence of 30 mM sodium chlorate, TFPI binding is unaffected, whereas the binding of bovine lipoprotein lipase, a protein known to associate with cell-surface GAGs, falls to 50% of control levels [29].
  • Finally, pretreatment of Sertoli cells with sodium chlorate, an inhibitor of cell surface proteoglycan sulfation, also retarded the decrease in recombinant IGFBP-3 [30].
  • We show that altering endogenous gradients of HS sulfation with sodium chlorate or over-O-sulfated synthetic heparin in lung organ cultures dramatically decreases Fgf10 binding [31].
  • The inhibitor of sulfation, sodium chlorate, vastly reduces PrPSc in ScN2a cells (Gabizon, R., Meiner, Z., Halimi, M., and Ben-Sasson, S. A. (1993) J. Cell. Physiol. 157, 319-325) [32].

Analytical, diagnostic and therapeutic context of sodium chlorate


  1. A27L protein mediates vaccinia virus interaction with cell surface heparan sulfate. Chung, C.S., Hsiao, J.C., Chang, Y.S., Chang, W. J. Virol. (1998) [Pubmed]
  2. Heparan sulfate proteoglycans play a dual role in regulating fibroblast growth factor-2 mitogenic activity in human breast cancer cells. Delehedde, M., Deudon, E., Boilly, B., Hondermarck, H. Exp. Cell Res. (1996) [Pubmed]
  3. Human papillomavirus 16 virus-like particles use heparan sulfates to bind dendritic cells and colocalize with langerin in Langerhans cells. Bousarghin, L., Hubert, P., Franzen, E., Jacobs, N., Boniver, J., Delvenne, P. J. Gen. Virol. (2005) [Pubmed]
  4. Chondroitin sulfate A chains enhance platelet derived growth factor-mediated signalling in fibrosarcoma cells. Fthenou, E., Zafiropoulos, A., Tsatsakis, A., Stathopoulos, A., Karamanos, N.K., Tzanakakis, G.N. Int. J. Biochem. Cell Biol. (2006) [Pubmed]
  5. Undersulfation of glycosaminoglycans induced by sodium chlorate treatment affects the progression of C6 rat glioma, in-vivo. Lobão-Soares, B., Alvarez-Silva, M., Mendes de Aguiar, C.B., Nicolau, M., Trentin, A.G. Brain Res. (2007) [Pubmed]
  6. Oncogenic Ras-induced proliferation requires autocrine fibroblast growth factor 2 signaling in skeletal muscle cells. Fedorov, Y.V., Rosenthal, R.S., Olwin, B.B. J. Cell Biol. (2001) [Pubmed]
  7. Evidence for the role of proteoglycans in cation-mediated gene transfer. Mislick, K.A., Baldeschwieler, J.D. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  8. Stable heparin-producing cell lines derived from the Furth murine mastocytoma. Montgomery, R.I., Lidholt, K., Flay, N.W., Liang, J., Vertel, B., Lindahl, U., Esko, J.D. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  9. Regulation of BMP7 expression during kidney development. Godin, R.E., Takaesu, N.T., Robertson, E.J., Dudley, A.T. Development (1998) [Pubmed]
  10. Expression of adhesion molecules by lp(a): a potential novel mechanism for its atherogenicity. Allen, S., Khan, S., Tam, S., Koschinsky, M., Taylor, P., Yacoub, M. FASEB J. (1998) [Pubmed]
  11. Effect of dietary mannanoligosaccharide and sodium chlorate on the growth performance, acute-phase response, and bacterial shedding of weaned pigs challenged with Salmonella enterica serotype Typhimurium. Burkey, T.E., Dritz, S.S., Nietfeld, J.C., Johnson, B.J., Minton, J.E. J. Anim. Sci. (2004) [Pubmed]
  12. Reduction of Campylobacter jejuni on chicken wings by chemical treatments. Zhao, T., Doyle, M.P. J. Food Prot. (2006) [Pubmed]
  13. Evaluation of chemicals used for drinking water disinfection for production of chromosomal damage and sperm-head abnormalities in mice. Meier, J.R., Bull, R.J., Stober, J.A., Cimino, M.C. Environmental mutagenesis. (1985) [Pubmed]
  14. Differential effect of cell-associated heparan sulfates on the binding of keratinocyte growth factor (KGF) and acidic fibroblast growth factor to the KGF receptor. Reich-Slotky, R., Bonneh-Barkay, D., Shaoul, E., Bluma, B., Svahn, C.M., Ron, D. J. Biol. Chem. (1994) [Pubmed]
  15. Self-catalyzed cyclization of the intervening sequence RNA of Tetrahymena: inhibition by methidiumpropyl.EDTA and localization of the major dye binding sites. Tanner, N.K., Cech, T.R. Nucleic Acids Res. (1985) [Pubmed]
  16. Detection of high-affinity intercalator sites in a ribosomal RNA fragment by the affinity cleavage intercalator methidiumpropyl-EDTA-iron(II). Kean, J.M., White, S.A., Draper, D.E. Biochemistry (1985) [Pubmed]
  17. Combinatorial determination of sequence specificity for nanomolar DNA-binding hairpin polyamides. Vashisht Gopal, Y.N., Van Dyke, M.W. Biochemistry (2003) [Pubmed]
  18. Under-sulfation by PAPS synthetase inhibition modulates the expression of ECM molecules during chondrogenesis. Cho, Y.R., Lee, S.J., Jeon, H.B., Park, Z.Y., Chun, J.S., Yoo, Y.J. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  19. Basic fibroblast growth factor binds its receptors, is internalized, and stimulates DNA synthesis in Balb/c3T3 cells in the absence of heparan sulfate. Fannon, M., Nugent, M.A. J. Biol. Chem. (1996) [Pubmed]
  20. Effect of chlorate on the sulfation of lipoprotein lipase and heparan sulfate proteoglycans. Sulfation of heparan sulfate proteoglycans affects lipoprotein lipase degradation. Hoogewerf, A.J., Cisar, L.A., Evans, D.C., Bensadoun, A. J. Biol. Chem. (1991) [Pubmed]
  21. Increased axon regeneration in astrocytes grown in the presence of proteoglycan synthesis inhibitors. Smith-Thomas, L.C., Stevens, J., Fok-Seang, J., Faissner, A., Rogers, J.H., Fawcett, J.W. J. Cell. Sci. (1995) [Pubmed]
  22. Roles of cellular activation and sulfated glycans in Haemophilus somnus adherence to bovine brain microvascular endothelial cells. Behling-Kelly, E., Vonderheid, H., Kim, K.S., Corbeil, L.B., Czuprynski, C.J. Infect. Immun. (2006) [Pubmed]
  23. Inhibition of the growth of a human nasopharyngeal carcinoma cell line by bFGF is mediated via FGFR-1. Chen, J.K., Chao, H.H., Yang, V.C. FASEB J. (1995) [Pubmed]
  24. Scavenger receptor class B, type I, mediates selective uptake of low density lipoprotein cholesteryl ester. Swarnakar, S., Temel, R.E., Connelly, M.A., Azhar, S., Williams, D.L. J. Biol. Chem. (1999) [Pubmed]
  25. Sequence-specific oxidative cleavage of DNA by a designed metalloprotein, Ni(II).GGH(Hin139-190). Mack, D.P., Dervan, P.B. Biochemistry (1992) [Pubmed]
  26. Evidence that heparin binding autocrine factors modulate testosterone production by the adult rat Leydig cell. McFarlane, J.R., Laslett, A., de Kretser, D.M., Risbridger, G.P. Mol. Cell. Endocrinol. (1996) [Pubmed]
  27. Alteration of matrix glycosaminoglycans diminishes articular chondrocytes' response to a canonical Wnt signal. Shortkroff, S., Yates, K.E. Osteoarthr. Cartil. (2007) [Pubmed]
  28. Oversulfated chondroitin/dermatan sulfates containing GlcAbeta1/IdoAalpha1-3GalNAc(4,6-O-disulfate) interact with L- and P-selectin and chemokines. Kawashima, H., Atarashi, K., Hirose, M., Hirose, J., Yamada, S., Sugahara, K., Miyasaka, M. J. Biol. Chem. (2002) [Pubmed]
  29. Glypican-3 is a binding protein on the HepG2 cell surface for tissue factor pathway inhibitor. Mast, A.E., Higuchi, D.A., Huang, Z.F., Warshawsky, I., Schwartz, A.L., Broze, G.J. Biochem. J. (1997) [Pubmed]
  30. Insulin-like growth factor-binding protein-3 (IGFBP-3) concentration in rat Sertoli cell-conditioned medium is regulated by a pathway involving association of IGFBP-3 with cell surface proteoglycans. Smith, E.P., Lu, L., Chernausek, S.D., Klein, D.J. Endocrinology (1994) [Pubmed]
  31. Heparan sulfates expressed in the distal lung are required for Fgf10 binding to the epithelium and for airway branching. Izvolsky, K.I., Zhong, L., Wei, L., Yu, Q., Nugent, M.A., Cardoso, W.V. Am. J. Physiol. Lung Cell Mol. Physiol. (2003) [Pubmed]
  32. Cellular heparan sulfate participates in the metabolism of prions. Ben-Zaken, O., Tzaban, S., Tal, Y., Horonchik, L., Esko, J.D., Vlodavsky, I., Taraboulos, A. J. Biol. Chem. (2003) [Pubmed]
  33. Heparanase uptake is mediated by cell membrane heparan sulfate proteoglycans. Gingis-Velitski, S., Zetser, A., Kaplan, V., Ben-Zaken, O., Cohen, E., Levy-Adam, F., Bashenko, Y., Flugelman, M.Y., Vlodavsky, I., Ilan, N. J. Biol. Chem. (2004) [Pubmed]
  34. Selective growth and distribution of crystalline enantiomers in hydrogels. Petrova, R.I., Swift, J.A. J. Am. Chem. Soc. (2004) [Pubmed]
  35. Improved method to measure erythrocyte filtration times increased extremely by chlorate. Steffen, C., Singelmann, E. Arch. Toxicol. (1983) [Pubmed]
  36. Role of cell surface glycosaminoglycans of human T cells in human immunodeficiency virus type-1 (HIV-1) infection. Ohshiro, Y., Murakami, T., Matsuda, K., Nishioka, K., Yoshida, K., Yamamoto, N. Microbiol. Immunol. (1996) [Pubmed]
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