β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons

Agata Copani, Daniela Melchiorri, Andrea Caricasole, Francesca Martini, Patrizio Sale, Roberto Carnevale, Roberto Gradini, Maria Angela Sortino, Luisa Lenti, Ruggero De Maria, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

We have shown that cortical neurons challenged with toxic concentrations of β-amyloid peptide (βAP) enter the S phase of the cell cycle before apoptotic death. Searching for a signaling molecule that lies at the border between cell proliferation and apoptotic death, we focused on the disialoganglioside GD3. Exposure of rat cultured cortical neurons to 25 μM βAP(25-35) induced a substantial increase in the intracellular levels of GD3 after 4 hr, a time that precedes neuronal entry into S phase. GD3 levels decreased but still remained higher than in the control cultures after 16 hr of exposure to βAP(25-35). Confocal microscopy analysis showed that the GD3 synthesized in response to βAP colocalized with nuclear chromatin. The increase in GD3 was associated with a reduction of sphingomyelin (the main source of the ganglioside precursor ceramide) and with the induction of α-2,8-sialyltransferase (GD3 synthase), the enzyme that forms GD3 from the monosialoganglioside GM3. A causal relationship between GD3, cell-cycle activation, and apoptosis was demonstrated by treating the cultures with antisense oligonucleotides directed against GD3 synthase. This treatment, which reduced βAP(25-35)-stimulated GD3 formation by ∼50%, abolished the neuronal entry into the S phase and was protective against β AP(25-35)-induced apoptosis.

Original languageEnglish
Pages (from-to)3963-3968
Number of pages6
JournalJournal of Neuroscience
Volume22
Issue number10
Publication statusPublished - May 15 2002

Fingerprint

Gangliosides
Amyloid
Cell Cycle
Apoptosis
Neurons
Peptides
S Phase
Sialyltransferases
Sphingomyelins
Antisense Oligonucleotides
Ceramides
Poisons
Confocal Microscopy
Chromatin
Cell Proliferation
Enzymes

Keywords

  • β-amyloid
  • Alzheimer's disease
  • Apoptosis
  • Cell cycle
  • Ganglioside GD3
  • Neurodegeneration

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Copani, A., Melchiorri, D., Caricasole, A., Martini, F., Sale, P., Carnevale, R., ... Nicoletti, F. (2002). β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons. Journal of Neuroscience, 22(10), 3963-3968.

β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons. / Copani, Agata; Melchiorri, Daniela; Caricasole, Andrea; Martini, Francesca; Sale, Patrizio; Carnevale, Roberto; Gradini, Roberto; Sortino, Maria Angela; Lenti, Luisa; De Maria, Ruggero; Nicoletti, Ferdinando.

In: Journal of Neuroscience, Vol. 22, No. 10, 15.05.2002, p. 3963-3968.

Research output: Contribution to journalArticle

Copani, A, Melchiorri, D, Caricasole, A, Martini, F, Sale, P, Carnevale, R, Gradini, R, Sortino, MA, Lenti, L, De Maria, R & Nicoletti, F 2002, 'β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons', Journal of Neuroscience, vol. 22, no. 10, pp. 3963-3968.
Copani A, Melchiorri D, Caricasole A, Martini F, Sale P, Carnevale R et al. β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons. Journal of Neuroscience. 2002 May 15;22(10):3963-3968.
Copani, Agata ; Melchiorri, Daniela ; Caricasole, Andrea ; Martini, Francesca ; Sale, Patrizio ; Carnevale, Roberto ; Gradini, Roberto ; Sortino, Maria Angela ; Lenti, Luisa ; De Maria, Ruggero ; Nicoletti, Ferdinando. / β-amyloid-Induced Synthesis of the Ganglioside Gd3 Is a Requisite for Cell Cycle Reactivation and Apoptosis in Neurons. In: Journal of Neuroscience. 2002 ; Vol. 22, No. 10. pp. 3963-3968.
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