Advertisement

Journal of Neural Transmission

, Volume 112, Issue 11, pp 1583–1590 | Cite as

High activity of acid sphingomyelinase in major depression

  • J. Kornhuber
  • A. Medlin
  • S. Bleich
  • V. Jendrossek
  • A. W. Henkel
  • J. Wiltfang
  • E. Gulbins
Rapid Communication

Summary.

Acid sphingomyelinase (A-SMase) and its reaction product ceramide may play a role in the pathophysiology of depressive disorders and in the therapeutic action of antidepressive drugs. In a prospective case-control study, A-SMase activity was measured in peripheral blood mononuclear cells of 17 patients with a major depressive episode who were free of antidepressant drug therapy for at least 10 days and 8 healthy volunteers. In the patient group, A-SMase activity was correlated to the score (n = 17, r = 0.64, P = 0.005). The patient group exhibited higher A-SMase activity compared to healthy volunteers (T = 2.09, df = 21.33, P<0.05). In addition, we demonstrate that the antidepressants imipramine and amitriptyline induce a long-term reduction of the activity of A-SMase in cultured cells.

Keywords: Major depression, ceramide, acid sphingomyelinase, sphingomyelin, receptor signaling. 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe, A, Shayman, JA 1998Purification and characterization of 1-O-acylceramide synthase, a novel phospholipase A2 with transacylase activity.J Biol Chem27384678474CrossRefPubMedGoogle Scholar
  2. Adams, PB, Lawson, S, Sanigorski, A, Sinclair, AJ 1996Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.Lipids31S157S161PubMedGoogle Scholar
  3. Akin, D, Manier, DH, Sanders-Bush, E, Shelton, RC 2005Signal transduction abnormalities in melancholic depression.Int J Neuropsychopharmacol8516CrossRefPubMedGoogle Scholar
  4. Albouz, S, Le Saux, F, Wenger, D, Hauw, JJ, Baumann, N 1986Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines.Life Sci38357363CrossRefPubMedGoogle Scholar
  5. Augé, N, Nègre-Salvayre, A, Salvayre, R, Levade, T 2000Sphingomyelin metabolites in vascular cell signaling and atherogenesis.Prog Lipid Res39207229CrossRefPubMedGoogle Scholar
  6. Besley, GT, Elleder, M 1986Enzyme activities and phospholipid storage patterns in brain and spleen samples from Niemann-Pick disease variants: a comparison of neuropathic and non-neuropathic forms.J Inherit Metab Dis95971CrossRefPubMedGoogle Scholar
  7. Coull, MA, Lowther, S, Katona, CLE, Horton, RW 2000Altered brain protein kinase C in depression: a post-mortem study.Eur Neuropsychopharmacol10283288CrossRefPubMedGoogle Scholar
  8. Dobrowsky, RT, Hannun, YA 1992Ceramide stimulates a cytosolic protein phosphatase.J Biol Chem26750485051PubMedGoogle Scholar
  9. Grassmé, H, Gulbins, E, Brenner, B, Ferlinz, K, Sandhoff, K, Harzer, K, Lang, F, Meyer, TF 1997Acidic sphingomyelinase mediates entry of N. gonorrhoeae into nonphagocytic cells.Cell91605615CrossRefPubMedGoogle Scholar
  10. Grassmé, H, Jekle, A, Riehle, A, Schwarz, H, Berger, J, Sandhoff, K, Kolesnick, R, Gulbins, E 2001CD95 signaling via ceramide-rich membrane rafts.J Biol Chem2762058920596CrossRefPubMedGoogle Scholar
  11. Gulbins, E, Bissonnette, R, Mahboubi, A, Martin, S, Nishioka, W, Brunner, T, Baier, G, Baier-Bitterlich, G, Byrd, C, Lang, F, Kolesnick, R, Altman, A, Green, D 1995FAS-induced apoptosis is mediated via a ceramide-initiated RAS signaling pathway.Immunity2341351CrossRefPubMedGoogle Scholar
  12. Gulbins, E, Szabo, I, Baltzer, K, Lang, F 1997Ceramide-induced inhibition of T lymphocyte voltage-gated potassium channel is mediated by tyrosine kinases.Proc Natl Acad Sci USA9476617666CrossRefPubMedGoogle Scholar
  13. Hannun, YA 1994The sphingomyelin cycle and the second messenger function of ceramide.J Biol Chem26931253128PubMedGoogle Scholar
  14. Heinrich, M, Wickel, M, Winoto-Morbach, S, Schneider-Brachert, W, Weber, T, Brunner, J, Saftig, P, Peters, C, Krönke, M, Schütze, S 2000Ceramide as an activator lipid of cathepsin D.Adv Exp Med Biol477305315PubMedGoogle Scholar
  15. Huwiler, A, Johansen, B, Skarstad, A, Pfeilschifter, J 2001Ceramide binds to the CaLB domain of cytosolic phospholipase A2 and facilitates its membrane docking and arachidonic acid release.FASEB J1579PubMedGoogle Scholar
  16. Johns, DG, Jin, JS, Wilde, DW, Webb, RC 1999Ceramide-induced vasorelaxation: an inhibitory action on protein kinase C.Gen Pharmacol33415421CrossRefPubMedGoogle Scholar
  17. Kölzer, M, Werth, N, Sandhoff, K 2004Interactions of acid sphingomyelinase and lipid bilayers in the presence of the tricyclic antidepressant desipramine.FEBS Lett5599698CrossRefPubMedGoogle Scholar
  18. Koumanov, KS, Momchilova, AB, Quinn, PJ, Wolf, C 2002Ceramides increase the activity of the secretory phospholipase A2 and alter its fatty acid specificity.Biochem J3634551CrossRefPubMedGoogle Scholar
  19. Latorre, E, Collado, MP, Fernández, I, Aragonés, MD, Catalán, RE 2003Signaling events mediating activation of brain ethanolamine plasmalogen hydrolysis by ceramide.Eur J Biochem2703646CrossRefPubMedGoogle Scholar
  20. Lepple-Wienhues, A, Belka, C, Laun, T, Jekle, A, Walter, B, Wieland, U, Welz, M, Heil, L, Kun, J, Busch, G, Weller, M, Bamberg, M, Gulbins, E, Lang, F 1999Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids.Proc Natl Acad Sci USA961379513800CrossRefPubMedGoogle Scholar
  21. Marathe, S, Kuriakose, G, Williams, KJ, Tabas, I 1999Sphingomyelinase, an enzyme implicated in atherogenesis, is present in atherosclerotic lesions and binds to specific components of the subendothelial extracellular matrix.Arterioscler Thromb Vasc Biol1926482658PubMedGoogle Scholar
  22. Müller, G, Ayoub, M, Storz, P, Rennecke, J, Fabbro, D, Pfizenmaier, K 1995PKC ζ is a molecular switch in signal transduction of TNF-α, bifunctionally regulated by ceramide and arachidonic acid.EMBO J1419611969PubMedGoogle Scholar
  23. Musselman, DL, Evans, DL, Nemeroff, CB 1998The relationship of depression to cardiovascular disease: epidemiology biology, and treatment.Arch Gen Psychiatry55580592CrossRefPubMedGoogle Scholar
  24. Nishizuka, Y 1992Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C.Science258607614PubMedGoogle Scholar
  25. Noponen, M, Sanfilipo, M, Samanich, K, Ryer, H, Ko, G, Angrist, B, Wolkin, A, Duncan, E, Rotrosen, J 1993Elevated PLA2 activity in schizophrenics and other psychiatric patients.Biol Psychiatry34641649CrossRefPubMedGoogle Scholar
  26. Nurmienen, TA, Holopainen, JM, Zhao, H, Kinnunen, PKJ 2002Observation of topical catalysis by sphingomyelinase coupled to microspheres.J Am Chem Soc1241212912134CrossRefPubMedGoogle Scholar
  27. Pandey, GN, Dwivedi, Y, Pandey, SC, Conley, RR, Roberts, RC, Tamminga, CA 1997Protein kinase C in the postmortem brain of teenage suicide victims.Neurosci Lett228111114CrossRefPubMedGoogle Scholar
  28. Pandey, GN, Dwivedi, Y, Rizavi, HS, Ren, X, Conley, RR 2004Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study.Arch Gen Psychiatry61685693CrossRefPubMedGoogle Scholar
  29. Pettus, BJ, Bielawska, A, Spiegel, S, Roddy, P, Hannun, YA, Chalfant, CE 2003Ceramide kinase mediates cytokine- and calcium ionophore-induced arachidonic acid release.J Biol Chem2783820638213CrossRefPubMedGoogle Scholar
  30. Riddle, EL, Rau, KS, Topham, MK, Hanson, GR, Fleckenstein, AE 2003Ceramide-induced alterations in dopamine transporter function.Eur J Pharmacol4583136CrossRefPubMedGoogle Scholar
  31. Ross, BM, Ward, P, Glen, I 2004Delayed vasodilatory response to methylnicotinate in patients with unipolar depressive disorder.J Affect Disord82285290CrossRefPubMedGoogle Scholar
  32. Sakuragawa, N, Sakuragaw, M, Kuwabara, T, Pentchev, PG, Barranger, JA, Brady, RO 1977Niemann-Pick disease experimental model: sphingomyelinase reduction induced by AY-9944.Science196317319PubMedGoogle Scholar
  33. Severus, WE, Ahrens, B, Stoll, AL 1999Omega-3 fatty acids – the missing link?Arch Gen Psychiatry56380381CrossRefPubMedGoogle Scholar
  34. Simons, K, Ikonen, E 1997Functional rafts in cell membranes.Nature387569572CrossRefPubMedGoogle Scholar
  35. Tanabe, F, Cui, SH, Ito, M 1998Ceramide promotes calpain-mediated proteolysis of protein kinase C β in murine polymorphonuclear leukocytes.Biochem Biophys Res Commun242129133CrossRefPubMedGoogle Scholar
  36. Westwick, JK, Bielawska, AE, Dbaibo, G, Hannun, YA, Brenner, DA 1995Ceramide activates the stress-activated protein kinases.J Biol Chem2702268922692CrossRefPubMedGoogle Scholar
  37. Zha, X, Pierini, LM, Leopold, PL, Skiba, PJ, Tabas, I, Maxfield, FR 1998Sphingomyelinase treatment induces ATP-independent endocytosis.J Cell Biol1403947CrossRefPubMedGoogle Scholar
  38. Zhang, Y, Yao, B, Delikat, S, Bayoumy, S, Lin, XH, Basu, S, McGinley, M, Chan-Hui, PY, Lichenstein, H, Kolesnick, R 1997Kinase suppressor of Ras is ceramide-activated protein kinase.Cell896372CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2005

Authors and Affiliations

  • J. Kornhuber
    • 1
  • A. Medlin
    • 2
  • S. Bleich
    • 1
  • V. Jendrossek
    • 3
  • A. W. Henkel
    • 1
  • J. Wiltfang
    • 1
  • E. Gulbins
    • 4
  1. 1.Department of PsychiatryUniversity of ErlangenGermany
  2. 2.Department of PsychiatryUniversity of GöttingenGermany
  3. 3.Department of Radiation OncologyUniversity of TübingenGermany
  4. 4.Department of Molecular BiologyUniversity of Duisburg-EssenGermany

Personalised recommendations