On the presence of C2-ceramide in mammalian tissues: possible relationship to etherphospholipids and phosphorylation by ceramide kinase
-
Helena Van Overloop
, Yves Denizot , Myriam Baes und Paul P. Van Veldhoven
Abstract
C2-ceramide (N-acetyl-sphingenine) is often used as an analog to study ceramide-mediated cellular processes. According to Lee et al. [J. Biol. Chem. 271 (1996), 209–217], C2-ceramide is formed by an acetyl transfer from platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) to sphingenine. To substantiate these unconfirmed findings, we (i) developed a method to quantify C2-ceramide and (ii) analyzed C2-ceramide levels in Pex5-/- mice, a model for Zellweger syndrome, in which the synthesis of ether lipids such as PAF is impaired. The presence of C2-ceramide could be established in brain (±10 pmol/g) and liver (±25 pmol/g) from control mice, and was approximately 5000-fold less than the main long-chain ceramide species. In Pex5-/- mice, C2-ceramide levels did not differ significantly compared to control tissues. Given the presence of a ceramide kinase in mammals, phosphorylation of C2-ceramide by human ceramide kinase (HsCERK) was tested. C2-ceramide appears to be a good substrate when albumin is used as carrier. In CHO cells overexpressing HsCERK, phosphorylation of exogenously added C2-ceramide could also be demonstrated. Our data indicate that C2-ceramide is present in mammalian tissues and can be converted to C2-ceramide-1-phosphate, in addition to other documented metabolic alterations, but does not seem to be linked to ether lipid metabolism.
References
Abe, A., Shayman, J.A., and Radin, N.S. (1996). A novel enzyme that catalyzes the esterification of N-acetylsphingosine. Metabolism of C2 ceramides. J. Biol. Chem.271, 14383–14389.10.1074/jbc.271.24.14383Suche in Google Scholar
Ardail, E., Popa, I., Bodennec, J., Famy, C., Loiusot, P., and Portoukalian, J. (2002). Subcellular distribution and metabolic fate of exogenous ceramides taken up by HL-60 cells. Biochim. Biophys. Acta1583, 305–310.10.1016/S1388-1981(02)00252-4Suche in Google Scholar
Bacchur, N.R. and Udenfriend, S. (1966). Microsomal synthesis of fatty acid amides. J. Biol. Chem.241, 1308–1313.10.1016/S0021-9258(18)96775-XSuche in Google Scholar
Bae, K., Longobardi, L., Karasawa, K., Malone, B., Inoue, T., Aoki, J., Arai, H., Inoue, K., and Lee, T. (2000). Platelet-activating factor (PAF)-dependent transacetylase and its relationship with PAF acetylhydrolases. J. Biol. Chem.275, 26704–26709.10.1016/S0021-9258(19)61433-XSuche in Google Scholar
Baes, M., Gressens, P., Baumgart, E., Carmeliet, P., Casteels, M., Fransen, M., Evrard, P., Fahimi, E., Declercq, P.E., Collen, D., et al. (1997). A mouse model for Zellweger syndrome. Nat. Genet.17, 49–56.10.1038/ng0997-49Suche in Google Scholar
Bayliss, M.A., Homer, R.B., and Shepherd, M.J. (1988). Determination of diethylene glycol in wine by high-performance liquid chromatography using anthracene-9-carbonyl chloride as a derivatizing reagent. J. Chromatogr.445, 403–408.10.1016/S0021-9673(01)84553-2Suche in Google Scholar
Bernardo, K., Hurwitz, R., Zenk, T., Desnick, R.J., Ferlinz, K., Schuchman, E., and Sandhoff, K. (1995). Purification, characterization, and biosynthesis of human acid ceramidase. J. Biol. Chem.270, 11098–11102.10.1074/jbc.270.19.11098Suche in Google Scholar
Bodennec, J., Koul, Aguado, I., Brichon, G., Zwingelstein, G., and Portoukalian, J. (2000). A procedure for fractionation of sphingolipid classes by solid-phase extraction on aminopropyl cartridges. J. Lipid Res.41, 1542–1530.10.1016/S0022-2275(20)33465-9Suche in Google Scholar
Causeret, C., Geeraert, L., Van der Hoeven, G., Mannaerts, G.P., and Van Veldhoven, P.P. (2000). Further characterization of rat dihydroceramide desaturase: tissue distribution, subcellular localization, and substrate specificity. Lipids35, 1117–1125.10.1007/s11745-000-0627-6Suche in Google Scholar PubMed
Das, A.K., Holmes, R.D., Wilson, G.N., and Hajra, A.K. (1992). Dietary ether lipid incorporation into tissue plasmalogens of humans and rodents. Lipids27, 401–405.10.1007/BF02536379Suche in Google Scholar PubMed
Denizot, Y., Gainant, A., Guglielmi, L., Bouvier, S., Cubertafond, P., and Mathonnet, M. (2003). Tissue concentrations of platelet-activating factor in colorectal carcinoma: inverse relationships with Dukes' stage of patients. Oncogene22, 7222–7224.10.1038/sj.onc.1207032Suche in Google Scholar
Dupuis, F., Levasseur, S., Jean-Louis, F., Dulery, C., Praloran, V., Denizot, Y., and Michel, L. (1997). Production, metabolism and effect of platelet-activating factor on the growth of the human K562 erythroid cell line. Biochim. Biophys. Acta1359, 241–249.10.1016/S0167-4889(97)00106-7Suche in Google Scholar
Futerman, A.H. and Hannun, Y.A. (2004). The complex life of simple sphingolipids. EMBO Rep.5, 777–782.10.1038/sj.embor.7400208Suche in Google Scholar
Gijsbers, S., Mannaerts, G.P., Himpens, B., and Van Veldhoven, P.P. (1999). N-Acetyl-sphingenine-1-phosphate is a potent calcium mobilizing agent. FEBS Lett.453, 269–272.10.1016/S0014-5793(99)00735-8Suche in Google Scholar
Gómez-Muñoz, A., Duffy, P.A., Martin, A., O'Brien, L., Byun, H.S., Bittman, R., and Brindley, D.N. (1995). Short chain ceramide-1-phosphates are novel stimulators of DNA synthesis and cell division: antagonism by cell-permeable ceramides. Mol. Pharmacol.47, 833–839.Suche in Google Scholar
Goto, J., Goto, N., Shamsa, F., Saito, M., Komatsu, S., Suzaki, K., and Nambara, T. (1983). New sensitive derivatization of hydroxysteroids for high-performance liquid chromatography with fluorescence detection. Anal. Chim. Acta147, 397–400.10.1016/0003-2670(83)80111-1Suche in Google Scholar
Hassler, D.F. and Bell, R.M. (1993). Ceramidases: enzymology and metabolic roles. Adv. Lipid Res.26, 49–57.Suche in Google Scholar
Hogback, S., Leppimaki, P., Rudnas, B., Bjorklund, S., Slotte, J.P., and Tornquist, K. (2003). Ceramide 1-phosphate increases intracellular free calcium concentrations in thyroid FRTL-5 cells: evidence for an effect mediated by inositol 1,4,5-trisphosphate and intracellular sphingosine 1-phosphate. Biochem. J.370, 111–119.10.1042/bj20020970Suche in Google Scholar
Iwamori, M, Costello, C., and Moser, H.W. (1979) Analysis and quantitation of free ceramide containing nonhydroxy and 2- hydroxy fatty acids, and phytosphingosine by high-performance liquid chromatography. J. Lipid Res.20, 86–96.10.1016/S0022-2275(20)40654-6Suche in Google Scholar
Janssen, A., Gressens, P., Grabenbauer, M., Baumgart, E., Schad, A., Vanhorebeek, I., Brouwers, A., Declercq, P.E., Fahimi, D., Evrard, P., et al. (2003). Neuronal migration depends on intact peroxisomal function in brain and in extraneuronal tissues. J. Neurosci.23, 9732–9741.10.1523/JNEUROSCI.23-30-09732.2003Suche in Google Scholar
Kashiwagi, M., Mikami, T., Chiba, M., Chiba, S., Matsumoto, H., Akino, T., and Gasa, S. (1997). Occurrence of nonenzymatic N-acetylation of sphinganine with acetyl coenzyme A producing C2-H2-ceramide and its inconvertibility to apoptotic C2-ceramide. Biochem. Mol. Biol. Intern.42, 1071–1080.10.1080/15216549700203531Suche in Google Scholar
King, C.M., Land, S.L., Jones, R.F., Debiec-Rychter, M., Lee, M.S., and Wang, C.Y. (1997). Role of acetyltransferases in the metabolism and carcinogenicity of aromatic amines. Mutat. Res.376, 123–128.10.1016/S0027-5107(97)00034-1Suche in Google Scholar
Komori, H. and Ito, M. (1995). Conversion of short chain ceramides to short chain ceramide GM3 in B16 melanoma cells. FEBS Lett.374, 299–302.10.1016/0014-5793(95)01137-4Suche in Google Scholar
Kunievsky, B. and Yavin, E. (1994). Production and metabolism of platelet-activating factor in the normal and ischemic fetal rat brain. J. Neurochem.63, 2144–2151.10.1046/j.1471-4159.1994.63062144.xSuche in Google Scholar
Lee, T.C., Ou, M.C, Shinozaki, K., Malone, B., and Snyder, F. (1996). Biosynthesis of N-acetylsphingosine by platelet-activating factor:sphingosine CoA-independent transacetylase in HL-60 cells. J. Biol. Chem.271, 209–217.10.1074/jbc.271.1.209Suche in Google Scholar
Levade, T., Malagarie-Cazenave, S., Gouaze, V., Segui, B., Tardy, C., Betito, S., Andrieu-Abadie, N., and Cuvillier, O. (2002). Ceramide in apoptosis: a revisited role. Neurochem. Res.27, 601–607.10.1023/A:1020215815013Suche in Google Scholar
Mannaerts, G.P. and Van Veldhoven, P.P. (1993). Metabolic pathways in mammalian peroxisomes. Biochimie75, 147–158.10.1016/0300-9084(93)90072-ZSuche in Google Scholar
Merrill, A.H. Jr., Sullards, M.C., Wang, E., Voss, K.A., and Riley, R.T. (2001) Sphingolipid metabolism: roles in signal transduction and disruption by fumonisins. Environ. Health Perspect.109, 283–289.Suche in Google Scholar
Montrucchio, G., Sapino, A., Bussolati, B., Ghisolfi, G., Rizea- Savu, S., Silvestro, L., Lupia, E., and Camussi, G. (1998). Potential angiogenic role of platelet-activating factor in human breast cancer. Am. J. Pathol.153, 1589–1596.10.1016/S0002-9440(10)65747-1Suche in Google Scholar
Murphy, R.C. (1993). Mass Spectrometry of Lipids (New York, USA: Plenum Press).Suche in Google Scholar
Nishida, K., Markey, S.P., Kustova, Y., Morse, H.C. III, Skolnick, P., Basile, A.S., and Sei, Y. (1996). Increased brain levels of platelet-activating factor in a murine acquired immune deficiency syndrome are NMDA receptor-mediated. J. Neurochem.66, 433–435.10.1046/j.1471-4159.1996.66010433.xSuche in Google Scholar PubMed
Noda, A., Ono, Y., Wu, X., Kudo, F., Jitsefuchi, N., Eto, S., and Noda, H. (1995). Determination and properties of acetyl conjugate of N-desisopropylpropanolol, AcDNP. Biol. Pharm. Bull.18, 1454–1455.10.1248/bpb.18.1454Suche in Google Scholar PubMed
Pettus, B.J., Baes, M., Busman, M., Hannun, Y.A., and Van Veldhoven, P.P. (2004). Mass spectrometric analysis of ceramide perturbations in brain and fibroblasts of mice and human patients with peroxisomal disorders. Rapid Commun. Mass Spectrom.18, 1569–1574.10.1002/rcm.1520Suche in Google Scholar PubMed
Prescott, S.M., Zimmerman, G.A., Stafforini, D.M., and McIntyre, T.M. (2000). Platelet-activating factor and related lipid mediators. Annu. Rev. Biochem.69, 419–445.10.1146/annurev.biochem.69.1.419Suche in Google Scholar PubMed
Ridgway, N.D. and Merriam, D.L. (1995). Metabolism of short chain ceramide and dihydroceramide analogues in Chinese hamster ovary (CHO) cells. Biochim. Biophys. Acta1256, 57–70.10.1016/0005-2760(95)00010-ASuche in Google Scholar
Sim, E., Payton, M., Noble, M., and Minchin, R. (2000). An update on genetic, structural and functional studies of arylamine N-acetyltransferases in eukaryotes and prokaryotes. Hum. Mol. Genet.9, 2435–2441.10.1093/hmg/9.16.2435Suche in Google Scholar
Snyder, F. (1990). Platelet-activating factor and related acetylated lipids as potent biologically active cellular mediators. Am. J. Physiol.259, C697–708.10.1152/ajpcell.1990.259.5.C697Suche in Google Scholar
Sturk, A., Schaap, M.C., Prins, A.J., ten Cate, W., Govaerts, L.C., Wanders, R.J.A., Heymans, H.S., and Schutgens, R.B. (1987). Age-related deficiency of the synthesis of platelet activating factor by leukocytes from Zellweger patients. Blood70, 460–463.10.1182/blood.V70.2.460.460Suche in Google Scholar
Suga, K., Kawasaki, T., Blank, M.L., and Snyder, F. (1990). An arachidonoyl (polyenoic)-specific phospholipase A2 activity regulates the synthesis of platelet-activating factor in granulocytic HL-60 cells. J. Biol. Chem.265, 12363–12371.10.1016/S0021-9258(19)38355-3Suche in Google Scholar
Sugiura, M., Kono, K., Liu, H., Shimizugawa, T., Minekura, H., Spiegel, S., and Kohama, T. (2002). Ceramide kinase, a novel lipid kinase. J. Biol. Chem.277, 23294–23300.10.1074/jbc.M201535200Suche in Google Scholar
Tiberghien, C., Laurent, L., Junier, M.P., and Dray, F. (1991). A competitive receptor binding assay for platelet-activating factor (PAF): quantification of PAF in rat brain. J. Lipid Mediat.3, 249–266.Suche in Google Scholar
Tornquist, K., Blom, T., Shariatmadari, R., and Pasternack, M. (2004). Ceramide 1-phosphate enhances calcium entry through voltage-operated calcium channels by a protein kinase C-dependent mechanism in GH4C1 rat pituitary cells. Biochem. J.380, 661–668.10.1042/bj20031637Suche in Google Scholar
Tserng, K.Y. and Griffin, R. (2003) Quantification and molecular species determination of diacylglycerols, phosphatidylcholines, ceramides, and sphingomyelins with gas chromatography. Anal. Biochem.323, 84–93.10.1016/j.ab.2003.08.026Suche in Google Scholar
Uemura, Y., Lee, T.C., and Snyder, F. (1991). A coenzyme A- independent transacylase is linked to the formation of platelet-activating factor (PAF) by generating the lyso-PAF intermediate in the remodeling pathway. J. Biol. Chem.266, 8268–8272.10.1016/S0021-9258(18)92972-8Suche in Google Scholar
Valsecchi, M., Mauri, L., Casellato, R., Prioni, S., Loberto, N., Prinetti, A., Chigorno, V., and Sonnino, S. (2006). Ceramide and sphingomyelin species of fibroblasts and neurons in culture. J. Lipid Res., in press, doi:10.1194/jlr.M600344-JLR200.10.1194/jlr.M600344-JLR200Suche in Google Scholar PubMed
Van Overloop, H., Gijbers, S., and Van Veldhoven, P.P. (2006). Further characterization of mammalian ceramide kinase: substrate delivery and (stereo)specificity, tissue distribution, and subcellular localization studies. J. Lipid Res.47, 268–283.10.1194/jlr.M500321-JLR200Suche in Google Scholar
Van Veldhoven, P.P. and Bell, R.M. (1988). Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells. Biochim. Biophys. Acta959, 185–196.10.1016/0005-2760(88)90030-6Suche in Google Scholar
Venable, M.E., Nieto, M.L., Schmitt, J.D., and Wykle, R.L. (1991). Conversion of 1-O-[3H]alkyl-2-arachidonoyl-sn-glycero-3- phosphorylcholine to lyso platelet-activating factor by the CoA-independent transacylase in membrane fractions of human neutrophils. J. Biol. Chem.266, 18691–18698.10.1016/S0021-9258(18)55118-8Suche in Google Scholar
Venable, M.E., Zimmerman, G.A., McIntyre, T.M., and Prescott, S.M. (1993). Platelet-activating factor: a phospholipid autacoid with diverse actions. J. Lipid Res.34, 691–702.10.1016/S0022-2275(20)39691-7Suche in Google Scholar
Wanders, R.J. (2004). Peroxisomes, lipid metabolism, and peroxisomal disorders. Mol. Genet. Metab.83, 16–27.10.1016/j.ymgme.2004.08.016Suche in Google Scholar PubMed
Yamaoka, S., Miyaji, M., Kitano, T., Umehara, H., and Okazaki, T. (2004). Expression cloning of a human cDNA restoring sphingomyelin synthesis and cell growth in sphingomyelin synthase-defective lymphoid cells. J. Biol. Chem.279, 18688–18693.10.1074/jbc.M401205200Suche in Google Scholar PubMed
©2007 by Walter de Gruyter Berlin New York
Artikel in diesem Heft
- Supplementary material to the paper “Evolutionary selection pressure and family relationships among connexin genes”
- Evolutionary selection pressure and family relationships among connexin genes
- Characterization of the large subunit of EcoHK31I methyltransferase by structural modeling and mutagenesis
- Purification, characterization, and molecular gene cloning of an antifungal protein from Ginkgo biloba seeds
- Maximal Ca2+i stimulation of cardiac Na+/Ca2+ exchange requires simultaneous alkalinization and binding of PtdIns-4,5-P2 to the exchanger
- A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue
- Properties and partial purification of sialate-O-acetyltransferase from bovine submandibular glands
- Raft association and lipid droplet targeting of flotillins are independent of caveolin
- On the presence of C2-ceramide in mammalian tissues: possible relationship to etherphospholipids and phosphorylation by ceramide kinase
- Specific inhibition of interleukin-13 activity by a recombinant human single-chain immunoglobulin domain directed against the IL-13 receptor α1 chain
- Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S
- Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease
- Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins
- Transgenic mouse brains for the evaluation and quality control of BSE tests
Artikel in diesem Heft
- Supplementary material to the paper “Evolutionary selection pressure and family relationships among connexin genes”
- Evolutionary selection pressure and family relationships among connexin genes
- Characterization of the large subunit of EcoHK31I methyltransferase by structural modeling and mutagenesis
- Purification, characterization, and molecular gene cloning of an antifungal protein from Ginkgo biloba seeds
- Maximal Ca2+i stimulation of cardiac Na+/Ca2+ exchange requires simultaneous alkalinization and binding of PtdIns-4,5-P2 to the exchanger
- A highly conserved protein secreted by the prostate cancer cell line PC-3 is expressed in benign and malignant prostate tissue
- Properties and partial purification of sialate-O-acetyltransferase from bovine submandibular glands
- Raft association and lipid droplet targeting of flotillins are independent of caveolin
- On the presence of C2-ceramide in mammalian tissues: possible relationship to etherphospholipids and phosphorylation by ceramide kinase
- Specific inhibition of interleukin-13 activity by a recombinant human single-chain immunoglobulin domain directed against the IL-13 receptor α1 chain
- Effects of disease-modifying anti-rheumatic drugs (DMARDs) on the activities of rheumatoid arthritis-associated cathepsins K and S
- Compartmentalised expression of meprin in small intestinal mucosa: enhanced expression in lamina propria in coeliac disease
- Human dipeptidyl peptidase III acts as a post-proline-cleaving enzyme on endomorphins
- Transgenic mouse brains for the evaluation and quality control of BSE tests