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 muM 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 similar to50%, abolished the neuronal entry into the S phase and was protective against betaAP(25-35)-induced apoptosis.

Beta-amyloid induced synthesis of the ganglioside GD3 is a requisite for cell cycle reactivation and apoptosis in neurons / A., Copani; Melchiorri, Daniela; A., Caricasole; F., Martini; Sale, Patrizio; Carnevale, Roberto; Gradini, Roberto; M. A., Sortino; Lenti, Luisa; R., De Maria; Nicoletti, Ferdinando. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - (2002), pp. 3963-3968.

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

MELCHIORRI, Daniela;SALE, PATRIZIO;CARNEVALE, Roberto;GRADINI, Roberto;LENTI, Luisa;NICOLETTI, Ferdinando
2002

Abstract

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 muM 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 similar to50%, abolished the neuronal entry into the S phase and was protective against betaAP(25-35)-induced apoptosis.
2002
beta-amyloid; GD3; apoptosis
01 Pubblicazione su rivista::01a Articolo in rivista
Beta-amyloid induced synthesis of the ganglioside GD3 is a requisite for cell cycle reactivation and apoptosis in neurons / A., Copani; Melchiorri, Daniela; A., Caricasole; F., Martini; Sale, Patrizio; Carnevale, Roberto; Gradini, Roberto; M. A., Sortino; Lenti, Luisa; R., De Maria; Nicoletti, Ferdinando. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - (2002), pp. 3963-3968.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/387805
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