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Research ArticleArticle

Attenuation of Cortical Neuronal Apoptosis by Gangliosides

Bo Rum Ryu, Dennis W. Choi, Dean M. Hartley, Erminio Costa, Ilo Jou and Byoung Joo Gwag
Journal of Pharmacology and Experimental Therapeutics August 1999, 290 (2) 811-816;
Bo Rum Ryu
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Dennis W. Choi
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Dean M. Hartley
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Erminio Costa
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Ilo Jou
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Byoung Joo Gwag
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Abstract

Addition of the natural gangliosides monosialoganglioside (GM1), disialoganglioside, trisialoganglioside, or tetrasialoganglioside in the range of 10 to 100 μM, but not asialoganglioside lacking the sialic acid moiety, attenuated cortical neuronal apoptosis induced by serum deprivation, ionomycin, or cyclosporin A but not by protein kinase inhibitors (staurosporine, genistein, lavendustin A, or herbimycin A). Coaddition of 100 nM wortmannin, a selective inhibitor of phosphatidylinositol 3-kinase, but not 1 μM Go6976, a selective protein kinase C inhibitor, blocked the neuroprotective effect of GM1. In contrast to its antiapoptotic effect, GM1 at up to 200 μM did not attenuate cortical neuronal necrosis induced by exposure to the excitotoxins N-methyl-d-aspartate or kainate. Furthermore, GM1 increased the necrosis induced by oxidative stress (addition of Fe2+ or buthionine sulfoximine). These data suggest that neuroprotective effects of natural gangliosides may preferentially reflect reduction of neuronal apoptosis rather than necrosis, and be mediated through mechanisms involving activation of phosphatidylinositol 3-kinase.

Footnotes

  • Send reprint requests to: Dr. Byoung Joo Gwag, Department of Pharmacology, Ajou University School of Medicine, Suwon, Kyungkido, Korea 442–749. E-mail: bjgwag{at}madang.ajou.ac.kr

  • ↵1 This work was supported by National Institute of Neurological Disorders and Stroke Grant NS 30337 (D.W.C.) and Korea Science and Engineering Foundation Grant 971-0704-021–2 (B.J.G.).

  • ↵2 Current address: Department of Neurology and Center for the Study of Nervous System Injury, Box 8111, Washington University School of Medicine, St. Louis, MO 63110.

  • ↵3 Current address: Center of Neurologic Diseases, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Boston, MA 02115.

  • ↵4 Current address: Psychiatric Institute, University of Illinois Medical School, Chicago, IL 60612.

  • Abbreviations:
    GM1
    monosialoganglioside
    BDNF
    brain-derived neurotrophic factor
    BSO
    buthionine sulfoximine
    GD1a
    disialoganglioside 1a
    GQ1b
    tetrasialoganglioside 1b
    GT1b
    trisialoganglioside 1b
    NMDA
    N-methyl-d-aspartate
    PI3-K
    phosphatidylinositol 3-kinase
    PKC
    protein kinase C
    MEM
    minimum essential medium
    DIV
    days in vitro
    LDH
    lactate dehydrogenase
    • Received September 8, 1998.
    • Accepted April 10, 1999.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 290 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 290, Issue 2
1 Aug 1999
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Research ArticleArticle

Attenuation of Cortical Neuronal Apoptosis by Gangliosides

Bo Rum Ryu, Dennis W. Choi, Dean M. Hartley, Erminio Costa, Ilo Jou and Byoung Joo Gwag
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 811-816;

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Research ArticleArticle

Attenuation of Cortical Neuronal Apoptosis by Gangliosides

Bo Rum Ryu, Dennis W. Choi, Dean M. Hartley, Erminio Costa, Ilo Jou and Byoung Joo Gwag
Journal of Pharmacology and Experimental Therapeutics August 1, 1999, 290 (2) 811-816;
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