Amyloid β-protein (Aβ) aggregation produces an oxidative stress in neuronal cells that, in turn, may induce an amyloidogenic shift of neuronal metabolism. To investigate this hypothesis, we analyzed intra- and extracellular Aβ content in NT2 differentiated cells incubated with 4-hydroxy-2,3-nonenal (HNE), a major product of lipid peroxidation. In parallel, we evaluated protein kinase C (PKC) isoenzymes activity, a signaling system suspected to modulate amyloid precursor protein (APP) processing. Low HNE concentrations (0.1-1 μM) induced a 2-6 fold increase of intracellular Aβ production that was concomitant with selective activation of βI and βII PKC isoforms, without affecting either cell viability or APP full-length expression. Selective activation of the same PRC isoforms was observed following NT2 differentiation. Our findings suggest that PKC β isoenzymes are part of cellular mechanisms that regulate production of the intracellular Aβ pool. Moreover, they indicate that lipid peroxidation fosters intracellular Aβ accumulation, creating a vicious neurodegenerative loop

Oxidative stress induces increase in intracellular amyloid-protein production and selective activation of I and II PKCs in NT2 cells

DOMENICOTTI, CINZIA MARIA;NITTI, MARIAPAOLA;BORGHI, ROBERTA;COTTALASSO, DAMIANO;ZACCHEO, DAMIANO;ODETTI, PATRIZIO;MARINARI, UMBERTO;TABATON, MASSIMO;PRONZATO, MARIA ADELAIDE
2000

Abstract

Amyloid β-protein (Aβ) aggregation produces an oxidative stress in neuronal cells that, in turn, may induce an amyloidogenic shift of neuronal metabolism. To investigate this hypothesis, we analyzed intra- and extracellular Aβ content in NT2 differentiated cells incubated with 4-hydroxy-2,3-nonenal (HNE), a major product of lipid peroxidation. In parallel, we evaluated protein kinase C (PKC) isoenzymes activity, a signaling system suspected to modulate amyloid precursor protein (APP) processing. Low HNE concentrations (0.1-1 μM) induced a 2-6 fold increase of intracellular Aβ production that was concomitant with selective activation of βI and βII PKC isoforms, without affecting either cell viability or APP full-length expression. Selective activation of the same PRC isoforms was observed following NT2 differentiation. Our findings suggest that PKC β isoenzymes are part of cellular mechanisms that regulate production of the intracellular Aβ pool. Moreover, they indicate that lipid peroxidation fosters intracellular Aβ accumulation, creating a vicious neurodegenerative loop
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11567/187929
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