title: Oxidative stress increases expression and activity of BACE in NT2 neurons.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tamagno
authors.forename: Paola
authors.initials: P
authors.lastname: Bardini
authors.forename: Alessandra
authors.initials: A
authors.lastname: Obbili
authors.forename: Antonella
authors.initials: A
authors.lastname: Vitali
authors.forename: Roberta
authors.initials: R
authors.lastname: Borghi
authors.forename: Damiano
authors.initials: D
authors.lastname: Zaccheo
authors.forename: Maria A
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Oliviero
authors.initials: O
authors.lastname: Danni
authors.forename: Mark A
authors.initials: MA
authors.lastname: Smith
authors.forename: George
authors.initials: G
authors.lastname: Perry
authors.forename: Massimo
authors.initials: M
authors.lastname: Tabaton
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis* / Q000378:metabolism; D010450:Endopeptidases; D004789:Enzyme Activation; D006801:Humans; D009474:Neurons / Q000201:enzymology*; D018384:Oxidative Stress / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000447:Aldehydes; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C027576:4-hydroxy-2-nonenal