A free radical-generating system regulates APP metabolism/processing |
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Authors: | Recuero María Muñoz Teresa Aldudo Jesús Subías Marta Bullido María J Valdivieso Fernando |
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Institution: | Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (U.A.M.-C.S.I.C.), Cantoblanco, 28049 Madrid, Spain Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain |
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Abstract: | Oxidative stress, a risk factor in the pathophysiology of Alzheimer’s disease, is intimately associated with aging. We previously reported that the X-XOD free radical generating system acts as a modulator of lipid metabolism and a mild inducer of apoptotic death. Using the same cell model, the present study examines the metabolism/processing of the amyloid precursor protein (APP). Prior to inducing cell death, X-XOD promoted the secretion of α-secretase-cleaved soluble APP (sAPPα) and increased the level of APP carboxy-terminal fragments produced by α and γ secretase (αCTF and γCTF/AICD). In contrast, it reduced the activity of β-secretase and the level of secreted Aβ. The present results indicate that mild oxidative stress maintained throughout culturing regulates APP metabolism/processing in SK-N-MC human neuroblastoma cells. |
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Keywords: | Aβ precursor protein β-Amyloid Carboxy-terminal fragments Free radical Oxidative stress Alzheimer&rsquo s disease |
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