Skip to main content
SpringerLink
Log in

Production of nerve growth factor enhanced in cultured mouse astrocytes by glycerophospholipids, sphingolipids, and their related compounds

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The NGF secretion from cultured mouse astrocytes was enhanced by sublethal concentrations of phosphatidic acid (PA), ceramide, or sphingosine (Sph), and concentration dependently by lysophosphatidic acid (LPA), sphingosylphosphorylcholine (SPC), or sphingosine-1-phosphate (S1P), but was unaffected by any concentrations of phosphatidylcholine (PC), phosphatidylethanolamine (PE) or sphingomyelin (SM). The enhancement of NGF synthesis by Sph was completely inhibited by the addition of ceramide synthase inhibitor, fumonisin B1. LPA and S1P showed similar hyperbolic curves with maximum NGF secretion at concentrations of more than 50 μM, but they showed no proliferative effect on quiescent astrocytes. The mechanisms underlying the stimulation of NGF synthesis by 50 μM LPA and 50 μM S1P were further investigated by using various inhibitors. One of the protein kinase C (PKC) inhibitors, Gö6976, suppressed the LPA- and S1P-stimulated NGF synthesis by 70 and 80%, respectively. LPA and S1P were found to activate common multiple signaling pathways for NGF production, involving the activation of the protein kinase C (PKC), mitogen-activated protein (MAP) kinase, and phosphatidylinositol 3-kinase (PI-3K) pathways.

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
Fig. 7

Similar content being viewed by others

References

  1. Weis C, Marksteiner J, Humpel C (2001) Nerve growth factor and glial cell line-derived neurotrophic factor restore the cholinergic neuronal phenotype in organotypic brain slices of the basal nucleus of Meynert. Neuroscience 102:129–138

    Article  PubMed  CAS  Google Scholar 

  2. Lad SP, Neet KE, Mufson EJ (2003) Nerve growth factor: structure, function and therapeutic implications for Alzheimer’s disease. Curr Drug Targets CNS Neurol Disord 2:315–334

    Article  PubMed  CAS  Google Scholar 

  3. Toyomoto M, Ohta M, Okumura K et al (2004) Prostaglandins are powerful inducers of NGF and BDNF production in mouse astrocyte cultures. FEBS Lett 562:211–215

    Article  PubMed  CAS  Google Scholar 

  4. Galve-Roperh I, Haro A, Diaz-Laviada I (1997) Induction of nerve growth factor synthesis by sphingomyelinase and ceramide in primary astrocyte cultures. Brain Res Mol Brain Res 52:90–97

    Article  PubMed  CAS  Google Scholar 

  5. Tabuchi S, Kume K, Aihara M et al (2000) Expression of lysophosphatidic acid receptor in rat astrocytes: mitogenic effect and expression of neurotrophic genes. Neurochem Res 25:573–582

    Article  PubMed  CAS  Google Scholar 

  6. Furukawa S, Furukawa Y, Satoyoshi E et al (1986) Synthesis and secretion of nerve growth factor by mouse astroglial cells in culture. Biochem Biophys Res Commun 136:57–63

    Article  PubMed  CAS  Google Scholar 

  7. Murase K, Takeuchi R, Furukawa S et al (1990) Highly sensitive enzyme immunoassay for beta-nerve growth factor (NGF): a tool for measurement of NGF level in rat serum. Biochem Int 22:807–813

    PubMed  CAS  Google Scholar 

  8. Merrill AH Jr., van Echten G, Wang E et al (1993) Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ. J Biol Chem 268:27299–27306

    PubMed  CAS  Google Scholar 

  9. Wattenberg EV, Badria FA, Shier WT (1996) Activation of mitogen-activated protein kinase by the carcinogenic mycotoxin fumonisin B1. Biochem Biophys Res Commun 227:622–627

    Article  PubMed  CAS  Google Scholar 

  10. Johnson KR, Johnson KY, Becker KP et al (2003) Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability. J Biol Chem 278:34541–34547

    Article  PubMed  CAS  Google Scholar 

  11. Eichholtz T, Jalink K, Fahrenfort I et al (1993) The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J 291:677–680

    PubMed  CAS  Google Scholar 

  12. Tokumura A, Iimori M, Nishioka Y et al (1994) Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta. Am J Physiol 267:C204–C210

    PubMed  CAS  Google Scholar 

  13. Caligan TB, Peters K, Ou J et al (2000) A high-performance liquid chromatographic method to measure sphingosine 1-phosphate and related compounds from sphingosine kinase assays and other biological samples. Anal Biochem 281:36–44

    Article  PubMed  CAS  Google Scholar 

  14. Anliker B, Chun J (2004) Lysophospholipid G protein-coupled receptors. J Biol Chem 279:20555–20558

    Article  PubMed  CAS  Google Scholar 

  15. Sorensen SD, Nicole O, Peavy RD et al (2003) Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol Pharmacol 64:1199–1209

    Article  PubMed  CAS  Google Scholar 

  16. McIntyre TM, Pontsler AV, Silva AR et al (2003) Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist. Proc Natl Acad Sci USA 100:131–136

    Article  PubMed  CAS  Google Scholar 

  17. Spiegel S, Milstien S (2003) Exogenous and intracellularly generated sphingosine 1-phosphate can regulate cellular processes by divergent pathways. Biochem Soc Trans 31:1216–1219

    Article  PubMed  CAS  Google Scholar 

  18. Thomson FJ, Clark MA (1995) Purification of a phosphatidic-acid-hydrolysing phospholipase A2 from rat brain. Biochem J 306:305–309

    PubMed  CAS  Google Scholar 

  19. Meyer zu Heringdorf D, Himmel HM, Jakobs KH (2002) Sphingosylphosphorylcholine-biological functions and mechanisms of action. Biochim Biophys Acta 1582:178–189

    PubMed  CAS  Google Scholar 

  20. Furukawa S, Furukawa Y, Satoyoshi E et al (1987) Synthesis/secretion of nerve growth factor is associated with cell growth in cultured mouse astroglial cells. Biochem Biophys Res Commun 142:395–402

    Article  PubMed  CAS  Google Scholar 

  21. Keller JN, Steiner MR, Holtsberg FW et al (1997) Lysophosphatidic acid-induced proliferation-related signals in astrocytes. J Neurochem 69:1073–1084

    Article  PubMed  CAS  Google Scholar 

  22. Ramakers GJ, Moolenaar WH (1998) Regulation of astrocyte morphology by RhoA and lysophosphatidic acid. Exp Cell Res 245:252–262

    Article  PubMed  CAS  Google Scholar 

  23. Pebay A, Toutant M, Premont J et al (2001) Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades. Eur J Neurosci 13:2067–2076

    Article  Google Scholar 

  24. Steiner MR, Urso JR, Klein J et al (2002) Multiple astrocyte responses to lysophosphatidic acids. Biochim Biophys Acta 1582:154–160

    PubMed  CAS  Google Scholar 

  25. Yamagata K, Tagami M, Torii Y et al (2003) Sphingosine 1-phosphate induces the production of glial cell line-derived neurotrophic factor and cellular proliferation in astrocytes. Glia 41:199–206

    Article  PubMed  Google Scholar 

  26. Tigyi G, Dyer DL, Miledi R (1994) Lysophosphatidic acid possesses dual action in cell proliferation. Proc Natl Acad Sci U S A 91:1908–1912

    Article  PubMed  CAS  Google Scholar 

  27. Fuentes E, Nadal A, McNaughton PA (1999) Lysophospholipids trigger calcium signals but not DNA synthesis in cortical astrocytes. Glia 28:272–276

    Article  PubMed  CAS  Google Scholar 

  28. Pebay A, Torrens Y, Toutant M et al (1999) Pleiotropic effects of lysophosphatidic acid on striatal astrocytes. Glia 28:25–33

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by a Grant-in-Aid for High Technology Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, 569-1094, Japan

    Atsushi Furukawa, Kouzou Kita, Misao Toyomoto, Shinobu Fujii, Seiji Inoue, Kyozo Hayashi & Kiyoshi Ikeda

  2. Department of Biochemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, 569-1094, Japan

    Seiji Inoue

Authors
  1. Atsushi Furukawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kouzou Kita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Misao Toyomoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shinobu Fujii
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seiji Inoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kyozo Hayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kiyoshi Ikeda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seiji Inoue.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Furukawa, A., Kita, K., Toyomoto, M. et al. Production of nerve growth factor enhanced in cultured mouse astrocytes by glycerophospholipids, sphingolipids, and their related compounds. Mol Cell Biochem 305, 27–34 (2007). https://doi.org/10.1007/s11010-007-9524-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9524-4

Keywords

Search

Navigation