Skip to main content

Advertisement

SpringerLink
Log in

Hypoxia remodels the composition of the constituent ceramide species of HexCer and Hex2Cer with phytosphingosine and hydroxy fatty acids in human colon cancer LS174T cells

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

Abstract

Oxygen-requiring enzymes, such as Δ4-desaturase (dihydroceramide desaturase), sphingolipid Δ4-desaturase/C-4-hydroxylase, and fatty acid 2-hydroxylase are involved in ceramide synthesis. We prepared free ceramides, sphingomyelins and glycosphingolipids (GSLs) from cancer cells cultivated under conditions of normoxia and hypoxia, and analyzed these compounds using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Human colon cancer LS174T cells were employed because these cells highly express hydroxyl fatty acids and phytosphingosine (t18:0) which are expected to be greatly influenced by changes in oxygen levels. As expected, the populations of dihydro-species of free ceramide and sphingomyelin with C16:0 non-hydroxy fatty acid were elevated, and the populations of HexCers and Hex2Cers, composed of C16:0 or C16:0 hydroxy fatty acid (C16:0h), and sphingosine (d18:1) or t18:0, were decreased under hypoxia. However, appreciable populations of HexCer and Hex2Cer species of C24:0 or C24:0h and t18:0 remained. These results suggest that the individual species of GSLs with fatty acids possessing different alkyl chain lengths, either non-hydroxy fatty acids or hydroxyl fatty acids, may be metabolized individually.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Nishimura, K.: Phytosphingosine is a characteristic component of the glycolipids in the vertebrate intestine. Comp. Biochem. Physiol. B 86, 149–154 (1987)

    CAS  PubMed  Google Scholar 

  2. Yoneshige, A., Sasaki, A., Miyazaki, M., Kojima, N., Suzuki, A., Matsuda, J.: Developmental changes in glycolipids and synchronized expression of nutrient transporters in the mouse small intestine. J. Nutr. Biochem. 21, 214–226 (2010)

    Article  CAS  PubMed  Google Scholar 

  3. Tanaka, K., Tamiya-Koizumi, K., Yamada, M., Murate, T., Kannagi, R., Kyogashima, M.: Individual profiles of free ceramide species and the constituent ceramide species of sphingomyelin and neutral glycosphingolipid and their alteration according to the sequential changes of environmental oxygen content in human colorectal cancer Caco-2 cells. Glycoconj. J. 31, 209–219 (2014)

    Article  CAS  PubMed  Google Scholar 

  4. Tanaka, K., Yamada, M., Tamiya-Koizumi, K., Kannagi, R., Aoyama, T., Hara, A., Kyogashima, M.: Systematic analyses of free ceramide species and ceramide species comprising neutral glycosphingolipids by MALDI-TOF MS with high-energy CID. Glycoconj. J. 28, 67–87 (2011)

    Article  CAS  PubMed  Google Scholar 

  5. Saito, T., Hakomori, S.I.: Quantitative isolation of total glycosphingolipids from animal cells. J. Lipid Res. 12, 257–259 (1971)

    CAS  PubMed  Google Scholar 

  6. Kyogashima, M., Tadano-Aritomi, K., Aoyama, T., Yusa, A., Goto, Y., Tamiya-Koizumi, K., Ito, H., Murate, T., Kannagi, R., Hara, A.: Chemical and apoptotic properties of hydroxy-ceramides containing long-chain bases with unusual alkyl chain lengths. J. Biochem. 144, 95–106 (2008)

    Article  CAS  PubMed  Google Scholar 

  7. Rylova, S.N., Somova, O.G., Zubova, E.S., Dudnik, L.B., Kogtev, L.S., Kozlov, A.M., Alesenko, A.V., Dyatlovitskaya, E.V.: Content and structure of ceramide and sphingomyelin and sphingomyelinase activity in mouse hepatoma-22. Biochemistry (Mosc) 64, 437–441 (1999)

    CAS  Google Scholar 

  8. Dyatlovitskaya, E.V., Kandyba, A.G., Kozlov, A.M., Somova, O.G.: Sphinganine in Sphingomyelins of tumors and mouse regenerating liver. Biochemistry (Mosc) 66, 502–504 (2001)

    Article  CAS  Google Scholar 

  9. Kyogashima, M., Taketomi, T.: Lipids from human platelets in primary thrombocythemia. Jpn. J. Exp. Med. 56, 113–118 (1986)

    CAS  PubMed  Google Scholar 

  10. Devlin, C.M., Lahm, T., Hubbard, W.C., Van Demark, M., Wang, K.C., Wu, X., Bielawska, A., Obeid, L.M., Ivan, M., Petrache, I.: Dihydroceramide-based response to hypoxia. J. Biol. Chem. 286, 38069–38078 (2011)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Domonand, B., Costello, C.E.: A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates. Glycoconj. J. 5, 397–409 (1988)

    Article  Google Scholar 

  12. Airley, R.E., Mobasheri, A.: Hypoxic regulation of glucose transport, anaerobic metabolism and angiogenesis in cancer: novel pathways and targets for anticancer therapeutics. Chemotherapy 53, 233–256 (2007)

    Article  CAS  PubMed  Google Scholar 

  13. Michel, C., van Echten-Deckert, G., Rother, J., Sandhoff, K., Wang, E., Merrill Jr., A.H.: Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide. J. Biol. Chem. 272, 22432–22437 (1997)

    Article  CAS  PubMed  Google Scholar 

  14. Ternes, P., Franke, S., Zahringer, U., Sperling, P., Heinz, E.: Identification and characterization of a sphingolipid delta4-desaturase family. J. Biol. Chem. 277, 25512–25518 (2002)

    Article  CAS  PubMed  Google Scholar 

  15. Mizutani, Y., Kihara, A., Igarashi, Y.: Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation. FEBS Lett. 563, 93–97 (2004)

    Article  CAS  PubMed  Google Scholar 

  16. Enomoto, A., Omae, F., Miyazaki, M., Kozutsumi, Y., Yubisui, T., Suzuki, A.: Dihydroceramide:sphinganine C-4-hydroxylation requires Des2 hydroxylase and the membrane form of cytochrome b5. Biochem. J. 397, 289–295 (2006)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Alderson, N.L., Rembiesa, B.M., Walla, M.D., Bielawska, A., Bielawski, J., Hama, H.: The human FA2H gene encodes a fatty acid 2-hydroxylase. J. Biol. Chem. 279, 48562–48568 (2004)

    Article  CAS  PubMed  Google Scholar 

  18. Kota, V., Hama, H.: 2′-Hydroxy ceramide in membrane homeostasis and cell signaling. Adv. Biol. Regul. 54, 223–230 (2014)

    Article  CAS  PubMed  Google Scholar 

  19. Kyogashima, M., Tamiya-Koizumi, K., Ehara, T., Li, G., Hu, R., Hara, A., Aoyama, T., Kannagi, R.: Rapid demonstration of diversity of sulfatide molecular species from biological materials by MALDI-TOF MS. Glycobiology 16, 719–728 (2006)

    Article  CAS  PubMed  Google Scholar 

  20. Tidhar, R., Futerman, A.H.: The complexity of sphingolipid biosynthesis in the endoplasmic reticulum. Biochim. Biophys. Acta 1833, 2511–2518 (2013)

    Article  CAS  PubMed  Google Scholar 

  21. Mizutani, Y., Kihara, A., Chiba, H., Tojo, H., Igarashi, Y.: 2-Hydroxy-ceramide synthesis by ceramide synthase family: enzymatic basis for the preference of FA chain length. J. Lipid Res. 49, 2356–2364 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. Hanada, K.: Intracellular trafficking of ceramide by ceramide transfer protein. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 86, 426–437 (2010)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Taniguchi, M., Okazaki, T.: The role of sphingomyelin and sphingomyelin synthases in cell death, proliferation and migration-from cell and animal models to human disorders. Biochim. Biophys. Acta 1841, 692–703 (2014)

    Article  CAS  PubMed  Google Scholar 

  24. Giussani, P., Colleoni, T., Brioschi, L., Bassi, R., Hanada, K., Tettamanti, G., Riboni, L., Viani, P.: Ceramide traffic in C6 glioma cells: evidence for CERT-dependent and independent transport from ER to the Golgi apparatus. Biochim. Biophys. Acta 1781, 40–51 (2008)

    CAS  PubMed  Google Scholar 

  25. Ishibashi, Y., Kohyama-Koganeya, A., Hirabayashi, Y.: New insights on glucosylated lipids: metabolism and functions. Biochim. Biophys. Acta 1831, 1475–1485 (2013)

    Article  CAS  PubMed  Google Scholar 

  26. Honke, K.: UDP-Gal: ceramide galactosyltransferase (UGT8). In: Taniguchi, N., Honke, K., Fukuda, M., et al. (eds.) Handbook of glycosyltransferases and related genes, pp. 131–140. Springer, Tokyo (2014)

  27. D’Angelo, G., Uemura, T., Chuang, C.C., Polishchuk, E., Santoro, M., Ohvo-Rekilä, H., Sato, T., Di Tullio, G., Varriale, A., D’Auria, S., Daniele, T., Capuani, F., Johannes, L., Mattjus, P., Monti, M., Pucci, P., Williams, R.L., Burke, J.E., Platt, F.M., Harada, A., De Matteis, M.A.: Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi. Nature 501, 116–120 (2013)

    Article  PubMed  Google Scholar 

  28. Yamaji, T., Hanada, K.: Sphingolipid metabolism and interorganellar transport: localization of sphingolipid enzymes and lipid transfer proteins. Traffic 16, 101–122 (2015)

    Article  CAS  PubMed  Google Scholar 

  29. Fabrias, G., Muñoz-Olaya, J., Cingolani, F., Signorelli, P., Casas, J., Gagliostro, V., Ghidoni, R.: Dihydroceramide desaturase and dihydrosphingolipids: debutant players in the sphingolipid arena. Prog. Lipid Res. 51, 82–94 (2012)

    Article  CAS  PubMed  Google Scholar 

  30. Hakomori, S.I.: Structure and function of glycosphingolipids and sphingolipids: recollections and future trends. Biochim. Biophys. Acta 1780, 325–346 (2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Karlsson, K.A.: Pathogen-host protein-carbohydrate interactions as the basis of important infections. Adv. Exp. Med. Biol. 491, 431–443 (2001)

    Article  CAS  PubMed  Google Scholar 

  32. Kannagi, R., Stroup, R., Cochran, N.A., Urdal, D.L., Young Jr., W.W., Hakomori, S.: Factors affecting expression of glycolipid tumor antigens: influence of ceramide composition and coexisting glycolipid on the antigenicity of gangliotriaosylceramide in murine lymphoma cells. Cancer Res. 43, 4997–5005 (1983)

    CAS  PubMed  Google Scholar 

  33. Kyogashima, M., Ginsburg, V., Krivan, H.C.: Escherichia coli K99 binds to N-glycolylsialoparagloboside and N-glycolyl-GM3 found in piglet small intestine. Arch. Biochem. Biophys. 270, 391–397 (1989)

    Article  CAS  PubMed  Google Scholar 

  34. Madar Johansson, M., Coddens, A., Benktander, J., Cox, E., Teneberg, S.: Porcine intestinal glycosphingolipids recognized by F6-fimbriated enterotoxigenic Escherichia coli. Microb. Pathog. 76, 51–60 (2014)

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Technology, Nagoya University Graduate School of Health Sciences, Daiko-Minami 1-1-20, Higashi-ku, Nagoya, 461-8673, Japan

    Kouji Tanaka, Keiko Tamiya-Koizumi & Takashi Murate

  2. Shimadzu Corporation, Nishinokyo-Kuwabaracho 1, Nakagyo-ku, Kyoto, 604-8511, Japan

    Masaki Yamada

  3. Research Complex for the Medicine Frontiers, Aichi Medical University, Yazako, Nagakute, Aichi, 480-1195, Japan

    Reiji Kannagi

  4. Department of Microbiology and Molecular Cell Biology, Nihon Pharmaceutical University, Komuro 10281, Inamachi, Saitama, 362-0806, Japan

    Mamoru Kyogashima

Authors
  1. Kouji Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keiko Tamiya-Koizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaki Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Takashi Murate
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Reiji Kannagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mamoru Kyogashima
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mamoru Kyogashima.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tanaka, K., Tamiya-Koizumi, K., Yamada, M. et al. Hypoxia remodels the composition of the constituent ceramide species of HexCer and Hex2Cer with phytosphingosine and hydroxy fatty acids in human colon cancer LS174T cells. Glycoconj J 32, 615–623 (2015). https://doi.org/10.1007/s10719-015-9607-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10719-015-9607-5

Keywords

Search

Navigation