A free radical-generating system regulates APP metabolism/processing.
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.
Recuero
María
M
Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (U.A.M.-C.S.I.C.), Cantoblanco, 28049 Madrid, Spain. mrecuero@cbm.uam.es
Muñoz
Teresa
T
Aldudo
Jesús
J
Subías
Marta
M
Bullido
María J
MJ
Valdivieso
Fernando
F
D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D019820:Xanthine / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D016564:Amyloid beta-Protein Precursor; D016166:Free Radical Scavengers; D005609:Free Radicals; D010446:Peptide Fragments; D019820:Xanthine; D014969:Xanthine Oxidase; D053829:Amyloid Precursor Protein Secretases