Abstract
Heparan sulfate (HS), is a proteoglycan (PG) found both in the extracellular matrix and on cell surface. It may represent one of the most biologically important glycoconjugates, playing an essential role in a variety of different events at molecular level. The publication of the mouse genome, and the intensive investigations aimed at understanding the proteome it encodes, has motivated us to initiate studies in mouse glycomics focused on HS. The current study is aimed at determining the quantitative and qualitative organ distribution of HS in mice. HS from brain, eyes, heart, lung, liver, kidney, spleen, intestine and skin was purified from 6–8 week old male and female mice. The recovered yield of HS from these organs is compared with the recovered whole body yield of HS. Structural characterization of the resulting HS relied on disaccharide analysis and 1H-NMR spectroscopy. Different organs revealed a characteristic HS structure. These data begin to provide a structural understanding of the role of HS in cell-cell interactions, cell signaling and sub-cellular protein trafficking as well as a fundamental understanding of certain aspects of protein-carbohydrate interactions.
Abbreviations
- GAGs:
-
glycosaminoglycans
- PG:
-
proteoglycans
- HS:
-
heparan sulfate
- SPR:
-
surface plasmon resonance
- MWCO:
-
molecular weight cut-off
- ΔUA-GlcNAc:
-
2-acetamido-2-deoxy-4-O-(4-deoxy-α-L-threo-hex-enepyranosyluronic acid)-D-glucose
- ΔUA-GlcNS:
-
2-deoxy-2-sulfamido-4-O-(4-deoxy-α-L-threo-hex-enepyranosyluronic acid)-D-glucose
- ΔUA-GlcNAc6S:
-
2-acetamido-2-deoxy-4-O-(4-deoxy-α-L-threo-hex-enepyranosyluronic acid)-6-O-sulfo- D-glucose
- ΔUA2S-GlcNAc:
-
2-acetamido-2-deoxy-4-O-(4-deoxy-2-O-sulfo-α-L-threo-hex-enepyranosyluronic acid)-D-glucose
- ΔUA-GlcNS6S:
-
2-deoxy-2-sulfamido-4-O-(4-deoxy-2-O-sulfo-α-L-threo-hex-enepyranosyluronic acid)-6-O-sulfo- D-glucose
- ΔUA2S-GlcNS:
-
2-deoxy-2-sulfamido-4-O-(4-deoxy-2-O-sulfo-α-L-threo-hex-enepyranosyluronic acid)-D-glucose
- ΔUA2S-GlcNAc6S:
-
2-acetamido-2-deoxy-4-O-(4-deoxy-2-O-sulfo-α-L-threo-hex-enepyranosyluronic acid)-6-O-sulfo-D-glucose
- ΔUA2S-GlcNS6S:
-
2-deoxy-2-sulfamido-4-O-(4-deoxy-2-O-sulfo-α-L-threo-hex-enepyranosyluronic acid)-6-O-sulfo- D-glucose
- CPC:
-
cetylpyridinium chloride
- COSY:
-
correlation spectroscopy
References
Capila, I., Linhardt, R.J.: Heparin – protein interactions. Angew. Chemie. Int. Ed. 41, 390–412 (2002)
Gomes, P.B., Dietrich, C.P.: Distribution of heparin and other sulfated glycosaminoglycans in vertebrates. Compar. Biochem. Physiol. 73, 857–63 (1982)
Dietrich, C.P., Nader, H.B., Straus, A.H.: Structural differences of heparan sulfates according to the tissue and species of origin. Biochem. Biophys. Res. Commun. 111, 865–71 (1983)
Medeiros, G.F., Mendes, A., Castro, R.A., Bau, E.C., Nader, H.B., Dietrich, C.P.: Distribution of sulfated glycosaminoglycans in the animal kingdom: widespread occurrence of heparin-like compounds in invertebrates. Biochim. Biophys. Acta 1475, 287–94 (2000)
Toyoda, H., Kinoshita-Toyoda, A., Selleck, S.: Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo. J. Biol. Chem. 275, 2269–75 (2000)
Turnbull, J., Drummond, K., Huang, Z., Kinnunen, T., Ford-Perriss, M., Murphy, M.,Guimond, S.: Heparan sulphate sulphotransferase expression in mice and Caenorhabditis elegans. Biochem. Soc. Trans. 31, 343–8 (2003)
Warda, M., Mao, W., Toida, T., Linhardt, R.J.: Turkey intestine as a commercial source of heparin? Comparative structural studies of intestinal avian and mammalian glycosaminoglycans. Comp. Biochem. Physiol. B. 134, 189–97 (2003)
Vongchan, P., Warda, M., Toyoda, H., Toida, T., Marks, R.M., Linhardt, R.J.: Structural characterization of human liver heparan sulfate. Biochim. Biophys. Acta. 1721, 1–8 (2005)
Warda, M., Linhardt, R.J.: Dromedary glycosaminoglycans: Molecular characterization of camel lung and liver heparan sulfate. Comp. Biochem. Phys. B 143, 37–43 (2006)
Warda, M., Gouda, E.M., Toida, T., Chi, L., Linhardt, R.J.: Isolation and characterization of raw heparin from dromedary intestine: evaluation of a new source of pharmaceutical heparin. Comp. Biochem. Physiol. C 136, 357–65 (2003)
Maccarana, M., Sakura, Y., Tawada, A., Yoshida, K., Lindahl, U.: Domain structure of heparan sulfates from bovine origin. J. Biol. Chem. 271, 17804–10 (1996)
Lindahl, B., Lindahl, U.: Amyloid-specific heparan sulfate from human liver and spleen. J. Biol. Chem. 272, 26091–4 (1997)
Ledin, J., Staatz, W., Li, J.-P., Götte, M., Selleck, S., Kjellén, L., Spillmann, D.: Heparan sulfate structure in mice with genetically modified heparan sulfate production. J. Biol. Chem. 279, 42732–41 (2004)
Rykova, V.I., Grigorieva, E.V.: Proteoglycan composition in cell nuclei of mouse hepatoma. Biochem. 63, 1271–6 (1998)
Esko, J.D., Selleck, S.B.: Order out of chaos: assembly of ligand binding sites in heparan sulfate. Ann. Rev. Biochem. 71, 435–71 (2002)
Yabe, T., Hata, T., He, J., Maeda, N.: Developmental and regional expression of heparan sulfate sulfotransferase genes in the mouse brain. Glycobiol. 15, 982–93 (2005)
Razi, N., Lindahl, U.: Biosynthesis of heparin/heparan sulfate. The D-glucosaminyl 3-O-sulfotransferase reaction: target and inhibitor saccharides. J. Biol. Chem. 270, 11267–75 (1995)
Gallagher, J.T., Turnbull, J.E., Lyon, M.: Patters of sulphation in heparan sulfate: Polymorphism based on a common structural theme. Int. J. Biochem. 24, 553–60 (1992)
Liu, J., Shworak, N.W., Sinaÿ P, Schwartz, J.J., Zhang, L., Fritze, LMS, Rosenberg, R.D.: Expression of heparan sulfate D-Glucosaminyl 3-O-Sulfotransferase isoforms reveals novel substrate specificities. J. Biol. Chem. 274, 5185–92 (1999)
Heinegard, D., Sommarin, Y.: Isolation and characterization of proteoglycans. Meth. Enzymol. 144, 319–72 (1987)
Furukawa, K., Terayama, H.: Isolation and identification of glycosaminoglycans associated with purified nuclei from rat liver. Biochim. Biophys. Acta. 499, 278–89 (1977)
Griffin, C.C., Linhardt, R.J., Van Gorp, C.L., Toida, T., Hileman, R.E., Schubert, R.L., Brown, S.E.: Isolation and characterization of heparan sulfate from crude porcine intestinal mucosa peptidoglycan heparin. Carbohydr. Res. 276, 183–97 (1995)
Toyoda, H., Kinoshita-Toyoda, A., Selleck, S.: Structural analysis of glycosaminoglycans in Drosophila and Caenorhabditis elegans and demonstration that tout-velu, a Drosophila gene related to EXT tumor suppressors, affects heparan sulfate in vivo. J. Biol. Chem. 275, 2269–75 (2000)
Imanari, T., Toida, T., Koshiishi, I., Toyoda, H.: High-performance liquid chromatographic analysis of glycosaminoglycan-derived oligosaccharides. J. Chromatogr. A 720, 275–93, (1996)
Sudo, M., Sato, K., Chaidedgumjorn, A., Toyoda, H., Toida, T., Imanari, T.: 1H nuclear magnetic resonance spectroscopic analysis for determination of glucuronic and iduronic acids in dermatan sulfate, heparin, and heparan sulfate. Anal. Biochem. 297, 42 –51 (2001)
Yu, G., LeBrun, L., Gunay, N.S., Hoppensteadt, D., Walenga, J., Fareed, J., Linhardt, R.J.: Heparinase I acts on a synthetic heparin pentasaccharide corresponding to the antithrombin III binding site. Thromb. Res. 100, 549–56 (2000)
Lei, P.S., Duchaussoy, P., Sizun, P., Mallet, J.M., Petitou, M., Sinaÿ, P.: Synthesis of a 3-deoxy-L-iduronic acid containing heparin pentasaccharide to probe the conformation of the antithrombin III binding sequence. Bioorg. Med. Chem. 6, 1337–46 (1998)
Desai, U.R., Petitou, M., Bjork, I., Olson, S.T.: Mechanism of heparin activation of antithrombin: evidence for an induced-fit model of allosteric activation involving two interaction subsites. Biochem. 37, 13033–41 (1998)
Bullock, S.L., Fletcher, J.M., Beddington, R.S., Wilson, V.A.: Renal agenesis in mice homozygous for a gene trap mutation in the gene encoding heparan sulfate 2-sulfotransferase. Genes & Developm. 12, 1894–1906 (1998)
HajMohammadi, S., Enjyoji, K., Princivalle, M., Christi, P., Lech, M., Beeler, D.L., Rayburn, H., Schwartz, J.J., Barzegar, S., de Agostini, A.I., Post, M.J., Rosenberg, R.D., Shworak, N.W.: Normal levels of anticoagulant heparan sulfate are not essential for normal hemostasis. J. Clin. Invest. 111, 989–99 (2003)
Araki, M., Takano, T., Uemonsa, T., Nakane, Y., Tsudzuki, M., Kaneko, T.: Epithelia-mesenchyme interaction plays an essential role in transdifferentiation of retinal pigment epithelium of silver mutant quail: localization of FGF and related molecules and aberrant migration pattern of neural crest cells during eye rudiment formation. Developm. Biol. 244, 358–71 (2002)
Goes, R.M., Laicine, E.M., Porcionatto, M.A., Bonciani Nader, H., Haddad, A.: Glycosaminoglycans in components of the rabbit eye: synthesis and characterization. Current Eye Res. 19, 146–53 (1999)
Auger, A., Truong, T.Q., Rhainds, D., Lapointe, J., Letarte, F., Brissette, L.: Low and high density lipoprotein metabolism in primary cultures of hepatic cells from normal and apolipoprotein E knockout mice. Eur. J. Biochem. 268, 2322–30 (2001)
Libeu, C.P., Lund-Katz, S., Phillips, M.C., Wehrli, S., Hernaiz, M.J., Capila, I., Linhardt, R.J., Raffai, R.L., Newhouse, Y.M., Zhou, F., Weisgraber, K.H.: New insights into the heparan sulfate proteoglycan-binding activity of apolipoprotein E. J. Biol. Chem. 276, 39138–44 (2001)
Hernáiz, M.J., Yang, H.O., Gunay, N.S., Linhardt, R.J.: Purification and Characterization of Heparan Sulfate Peptidoglycans from Bovine Liver. Carbohydr. Polym. 48, 153–60 (2002)
Chen, Y., Maguire, T., Hileman, R.E., Fromm, J.R., Esko, J.D., Linhardt, R.J., Marks, R.M.: Dengue Virus Infectivity Depends on Envelope Protein Binding to Target Cell Heparan Sulfate. Nat. Med. 3, 866–71 (1997)
Rathore, D., McCutchan, T.F., Hernáiz, M.J., LeBrun, L.A., Lang, S.C., Linhardt, R.J.: Direct Measurement of the Interaction of Glycosaminoglycans and a Heparin Decasaccharide with Malaria Circumsporozoite Protein. Biochemistry 40, 11518–24 (2001)
Rathore, D., Hrstka, SCL, Sacci, J.B., de la Vega, P., Linhardt, R.J., Kumar, S., McCutchan, T.F.: Molecular Mechanism of Host Specificity in Plasmodium falciparum Infection: Role of Circumsporozoite Protein. J. Biol. Chem. 278, 40905–10 (2003)
Kisilevsky, R., Szarek, W.A.: Novel glycosaminoglycan precursors as anti-amyloid agents part II. J. Molec. Neurosci. 19, 45–50 (2002)
Uchimura, K., Kadomatsu, K., Nishimura, H., Muramatsu, H., Nakamura, E., Kurosawa, N., Habuchi, O., El-Fasakhany, F.M., Yoshikai, Y., Muramatsu, T.: Functional analysis of the chondroitin 6-sulfotransferase gene in relation to lymphocyte subpopulations, brain development, and oversulfated chondroitin sulfates. J. Biol. Chem. 277, 1443–50 (2002)
Park, Y., Yu, G., Gunay, N.S., Linhardt, R.J.: Purification and Characterization of Heparan Sulphate Proteoglycan from Bovine Brain. Biochem. J. 344, 723–30 (1999)
Kinnunen, T., Raulo, E., Nolo, R., Maccarana, M., Lindahl, U., Rauvala, H.: Neurite outgrowth in brain neurons induced by heparin-binding growth-associated molecule (HB-GAM) depends on the specific interaction of HB-GAM with heparan sulfate at the cell surface. J. Biol. Chem. 271, 2243–8 (1996)
Maresh, G.A., Erezyilmaz, D., Murry, C.E., Nochlin, D., Snow, A.D.: Detection and quantitation of perlecan mRNA levels in Alzheimer’s disease and normal aged hippocampus by competitive reverse transcription-polymerase chain reaction. J. Neurochem. 67, 1132–44 (1996)
Toida, T., Yoshida, H., Toyoda, H., Koshiishi, I., Imanari, T., Hileman, R.E., Fromm, J.R., Linhardt, R.J.: Structural differences and the presence of unsubstituted amino groups in heparan sulphates from different tissues and species. Biochem. J. 322, 499–506 (1997)
Linhardt, R.J., Toida, T.: Role of Glycosaminoglycans in Cellular Communication. Acc. Chem. Res. 37, 431–8 (2004)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Warda, M., Toida, T., Zhang, F. et al. Isolation and characterization of heparan sulfate from various murine tissues. Glycoconj J 23, 555–563 (2006). https://doi.org/10.1007/s10719-006-7668-1
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10719-006-7668-1