Neurobiology of Disease (Aug 2002)
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons
- Elena Tamagno,
- Paola Bardini,
- Alessandra Obbili,
- Antonella Vitali,
- Roberta Borghi,
- Damiano Zaccheo,
- Maria A. Pronzato,
- Oliviero Danni,
- Mark A. Smith,
- George Perry,
- Massimo Tabaton
Affiliations
- Elena Tamagno
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Paola Bardini
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Alessandra Obbili
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Antonella Vitali
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Roberta Borghi
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Damiano Zaccheo
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Maria A. Pronzato
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Oliviero Danni
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Mark A. Smith
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- George Perry
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Massimo Tabaton
- Department of Experimental Medicine and Oncology, General Pathology Section, University of Turin, Turin, Italy; Department of Experimental Medicine, Human Anatomy Section, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, Department of Experimental Medicine, General Pathology Section, University of Genova, Genova, Italy; Human Anatomy Section, General Pathology Section, Department of Neurological Sciences and Vision, University of Genova, Genova, Italy; Institute of Pathology, Case Western Reserve University, Cleveland, Ohio
- Journal volume & issue
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Vol. 10,
no. 3
pp. 279 – 288
Abstract
Recently an aspartyl protease with β-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 NT2 neurons to the two classical pro-oxidant stimuli ascorbate/FeSO4 and H2O2/FeSO4 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 α-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 Aβ production are strictly interrelated events and suggest that inhibition of BACE may have a therapeutic effect synergic with antioxidant compounds.
