RGD Reference Report - Beta-amyloid-induced synthesis of the ganglioside GD3 is a requisite for cell cycle reactivation and apoptosis in neurons. - Rat Genome Database

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Beta-amyloid-induced synthesis of the ganglioside GD3 is a requisite for cell cycle reactivation and apoptosis in neurons.

Authors: Copani, A  Melchiorri, D  Caricasole, A  Martini, F  Sale, P  Carnevale, R  Gradini, R  Sortino, MA  Lenti, L  De Maria, R  Nicoletti, F 
Citation: Copani A, etal., J Neurosci 2002 May 15;22(10):3963-8.
RGD ID: 625459
Pubmed: PMID:12019315   (View Abstract at PubMed)
PMCID: PMC6757645   (View Article at PubMed Central)
DOI: DOI:20026378   (Journal Full-text)

We have shown that cortical neurons challenged with toxic concentrations of beta-amyloid peptide (betaAP) 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 microm betaAP(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 betaAP(25-35). Confocal microscopy analysis showed that the GD3 synthesized in response to betaAP 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 alpha-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 betaAP(25-35)-stimulated GD3 formation by approximately 50%, abolished the neuronal entry into the S phase and was protective against betaAP(25-35)-induced apoptosis.

Objects referenced in this article
Gene St8sia1 ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 Rattus norvegicus

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