Oxidative stress increases expression and activity of BACE in NT2 neurons

• Published in: Neurobiology of disease Vol. 10; no. 3; pp. 279 - 288
• Main Authors: Tamagno, Elena, Bardini, Paola, Obbili, Alessandra, Vitali, Antonella, Borghi, Roberta, Zaccheo, Damiano, Pronzato, Maria A, Danni, Oliviero, Smith, Mark A, Perry, George, Tabaton, Massimo
• Format: Journal Article
• Language: English
• Published: United States Elsevier 01.08.2002
• Subjects: Aldehydes - metabolism; Alzheimer's disease; Amyloid Precursor Protein Secretases; Aspartic Acid Endopeptidases - biosynthesis; Aspartic Acid Endopeptidases - metabolism; BACE; Endopeptidases; Enzyme Activation; HNE; Humans; Neurons - enzymology; NT2 neurons; oxidative stress; Oxidative Stress - physiology; Tumor Cells, Cultured
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1006/nbdi.2002.0515

Recently an aspartyl protease with beta-secretase activity called BACE was identified. In the present paper we showed that BACE is modulated by the oxidative stress product 4-hydroxynonenal (HNE). Exposure of NT(2) neurons to the two classical pro-oxidant stimuli ascorbate/FeSO(4) and H(2)O(2)/FeSO(4) resulted in a significant generation of HNE, which is temporally followed by an increased production of BACE protein levels. HNE mediated BACE induction is accompanied by a proportional elevation of carboxy-terminal fragments of amyloid precursor protein. Moreover, the direct relationship between BACE induction and lipid peroxidation products was strongly confirmed by the protection exerted by a short pretreatment with alpha-tocopherol, the most important antioxidant known to prevent the formation of aldehydic end-products of lipid peroxidation, including HNE. Our results support the hypothesis that oxidative stress and A beta production are strictly interrelated events and suggest that inhibition of BACE may have a therapeutic effect synergic with antioxidant compounds.