Sphingolipids Metabolism Following Cerebral Ischemia

  • Masaru Kubota
  • Makoto Nakane
  • Tadayoshi Nakagomi
  • Hitoshi Nakayama
  • Akira Tamura
  • Harumi Hisaki
  • Hiroyuki Shimasaki
  • Nobuo Ueta
Conference paper

Abstract

It has been well known that ischemic insults induced the hydrolytic breakdown of polyphosphoinositides by calcium-dependent phospholipase C, and diacylglycerol (DAG) was hydrolyzed to free fatty acids (FFAs) by DAG lipase [1, 2, 11, 22, 26]. The composition of FFAs consists mainly of stearic (C18:0) and arachidonic acids (C20:4). These processes are thought to act at early phase of the ischemia. Prolonged ischemia induces the degradation of membrane phospholipids, and the level of various phospholipids decrease at late phase of the ischemia. To determine a therapeutic time window of the ischemic penumbra, it is essential to evaluate the time course of the degradation of glycerophospholipids.

Key words

Rat focal ischemia gerbil global ischemia membrane lipids sphingomyelin ceramide 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Abe K, Kogure K, Yamamoto H, Imazawa M, Miyamoto K (1987) Mechanism of arachidonic acid liberation during ischemia in gerbil cerebral cortex. J Neurochem 48:503–509PubMedCrossRefGoogle Scholar
  2. 2.
    Bazan NGJ (1970) Effects of ischemia and electroconvulsive shock on free fatty acid pool in the brain. Biochim Biophys Acta 218:1–10PubMedCrossRefGoogle Scholar
  3. 3.
    Brugg B, Michel PP, Agid Y, Ruberg M (1996) Ceramide induces apoptosis in cultured mesen-cephalic neurons. J Neurochem 66:733–739PubMedCrossRefGoogle Scholar
  4. 4.
    Casaccia-Bonnefil P, Aibel L, Chao MV (1996) Central glial and neuronal populations display differential sensitivity to ceramide-dependent cell death. J Neurosci Res 43:382–389PubMedCrossRefGoogle Scholar
  5. 5.
    Folch J, Lees M, Sloane-Stanley GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497–509PubMedGoogle Scholar
  6. 6.
    Hannun YA (1996) Functions of ceramide in coordinating cellular responces to stress. Science 24:1855–1859CrossRefGoogle Scholar
  7. 7.
    Hannun YA, Loomis CR, Merrill AHJ, Bell RM (1986) Sphingosine inhibition of protein kinase C activity and phorbol dibutyrate binding in vitro and in human platelets. J Biol Chem 261:12604–12609PubMedGoogle Scholar
  8. 8.
    Hara A, Taketomi T (1983) Detection of D-erythro and L-threo sphingosine bases in preparative sphingosylphosphorylcholine and its N-acylated derivatives and some evidence of their different chemical configurations. J Biochem 94:1715–1718PubMedGoogle Scholar
  9. 9.
    Harel R, Futerman AH (1993) Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons. J Biol Chem 268:14476–14481PubMedGoogle Scholar
  10. 10.
    Hauser G, Eichberg J, Gonzalez-Sastre F (1971) Regional distribution of polyphosphoinositides in rat brain. Biochim Biophys Acta 248:87–95PubMedCrossRefGoogle Scholar
  11. 11.
    Ikeda M, Yoshida S, Busto R, Santiso M, Ginsberg MD (1986) Polyphosphoinositides as a probable source of brain free fatty acids accumulated at the onset of ischemia. J Neurochem 47:123–132PubMedCrossRefGoogle Scholar
  12. 12.
    Jayadev S, Linardic CM, Hannun YA (1994) Identification of arachidonic acid as a mediator of sphingomyelin hydrolysis in response to tumor necrosis factor. J Biol Chem 269:5757–5763PubMedGoogle Scholar
  13. 13.
    Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239:57–69PubMedCrossRefGoogle Scholar
  14. 14.
    Kitagawa K, Matsumoto M, Tagaya M, Hata R, Ueda H, Niinobe M, Handa N, Fukunaga R, Kimura K, Mikoshiba K, Kamada T (1990) Ischemic tolerance’ phenomenon found in the brain. Brain Res 528:21–24PubMedCrossRefGoogle Scholar
  15. 15.
    Kubota M, Nakane M, Narita K, Nakagomi T, Tamura A, Hisaki H, Shimasaki H, Ueta N (1998) Mild hypothermia reduces the rate of metabolism of arachidonic acid following postischemic reperfusion. Brain Res 779:297–300PubMedCrossRefGoogle Scholar
  16. 16.
    Kubota M, Narita K, Nakagomi T, Tamura A, Shimasaki H, Ueta N, Yoshida S (1996) Sphingomyelin changes in rat cerebral cortex during focal ischemia. Neurol Res 18:337–341PubMedGoogle Scholar
  17. 17.
    Lee C, Hajra AK (1991) Molecular species of diacylglycerols and phosphoglycerides and the postmortem changes in the molecular species of diacylglycerols in rat brains. J Neurochem 56:370–379PubMedCrossRefGoogle Scholar
  18. 18.
    Nakano S, Kogure K, Abe K, Yae T (1990) Ischemia-induced alterations in lipid metabolism of the gerbil cerebral cortex: I. Changes in free fatty acid liberation. J Neurochem 54:1911–1916PubMedCrossRefGoogle Scholar
  19. 19.
    Nitatori T, Sato N, Waguri S, Karasawa Y, Araki H, Shibanai K, Kominami E, Uchiyama Y (1995) Delayed neuronal death in the CAl pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. J Neurosci 15:1001–1011PubMedGoogle Scholar
  20. 20.
    Obeid LM, Linardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259:1769–1771PubMedCrossRefGoogle Scholar
  21. 21.
    Schwarz A, Futerman AH (1997) Distinct roles for ceramide and glucosylceramide at different stages of neuronal growth. J Neurosci 17:2929–2938PubMedGoogle Scholar
  22. 22.
    Siesjo BK, Katsura K, Zhao Q, Folbergrova J, Pahlmark K, Siesjo P, Smith ML (1995) Mechanisms of secondary brain damage in global and focal ischemia: a speculative synthesis. J Neurotrauma 12:943–956PubMedCrossRefGoogle Scholar
  23. 23.
    Stoffel W, Melzner I (1980) Studies in vitro on the biosynthesis of ceramide and sphingomyelin. A re-evaluation of proposed pathways. Hoppe-Seyler’s Z Physiol Chem 361:755–771PubMedCrossRefGoogle Scholar
  24. 24.
    Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischaemia in the rat: 1. Description of technique and early neuropathological consequences following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1:53–60PubMedCrossRefGoogle Scholar
  25. 25.
    Tamura A, Graham DI, McCulloch J, Teasdale GM (1981) Focal cerebral ischaemia in the rat: 2. Regional cerebral blood flow determined by [14Cliodoantipyrine autoradiography following middle cerebral artery occlusion. J Cereb Blood Flow Metab 1:61–69PubMedCrossRefGoogle Scholar
  26. 26.
    Yoshida S, Inoh S, Asano T, Sano K, Kubota M, Shimazaki H, Ueta N (1980) Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain: Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg 53:323–331PubMedCrossRefGoogle Scholar
  27. 27.
    Yoshida S, Inoh S, Asano T, Sano K, Kubota M, Shimazaki H, Ueta N (1980) Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg 53:323–331PubMedCrossRefGoogle Scholar
  28. 28.
    Zhang JP, Sun GY (1995) Free fatty acids, neutral glycerides, and phosphoglycerides in transient focal cerebral ischemia. J Neurochem 64:1688–1695PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Masaru Kubota
    • 1
  • Makoto Nakane
    • 2
  • Tadayoshi Nakagomi
    • 2
  • Hitoshi Nakayama
    • 1
  • Akira Tamura
    • 2
  • Harumi Hisaki
    • 3
  • Hiroyuki Shimasaki
    • 3
  • Nobuo Ueta
    • 3
  1. 1.Department of Neurosurgery, University HospitalUniversity School of MedicineMizonokuchiTeikyo
  2. 2.Department of NeurosurgeryTeikyo
  3. 3.First Department of Biochemistry, Teikyo UniversitySchool of MedicineTeikyo

Personalised recommendations