Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons
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 i...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2002-08-01
|
| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996102905152 |
| id |
doaj-9f2bf446cb9a48cfb665296275e4ef51 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Elena Tamagno Paola Bardini Alessandra Obbili Antonella Vitali Roberta Borghi Damiano Zaccheo Maria A. Pronzato Oliviero Danni Mark A. Smith George Perry Massimo Tabaton |
| spellingShingle |
Elena Tamagno Paola Bardini Alessandra Obbili Antonella Vitali Roberta Borghi Damiano Zaccheo Maria A. Pronzato Oliviero Danni Mark A. Smith George Perry Massimo Tabaton Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons Neurobiology of Disease BACE Alzheimer's disease HNE NT2 neurons oxidative stress |
| author_facet |
Elena Tamagno Paola Bardini Alessandra Obbili Antonella Vitali Roberta Borghi Damiano Zaccheo Maria A. Pronzato Oliviero Danni Mark A. Smith George Perry Massimo Tabaton |
| author_sort |
Elena Tamagno |
| title |
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons |
| title_short |
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons |
| title_full |
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons |
| title_fullStr |
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons |
| title_full_unstemmed |
Oxidative Stress Increases Expression and Activity of BACE in NT2 Neurons |
| title_sort |
oxidative stress increases expression and activity of bace in nt2 neurons |
| publisher |
Elsevier |
| series |
Neurobiology of Disease |
| issn |
1095-953X |
| publishDate |
2002-08-01 |
| description |
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. |
| topic |
BACE Alzheimer's disease HNE NT2 neurons oxidative stress |
| url |
http://www.sciencedirect.com/science/article/pii/S0969996102905152 |
| work_keys_str_mv |
AT elenatamagno oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT paolabardini oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT alessandraobbili oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT antonellavitali oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT robertaborghi oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT damianozaccheo oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT mariaapronzato oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT olivierodanni oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT markasmith oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT georgeperry oxidativestressincreasesexpressionandactivityofbaceinnt2neurons AT massimotabaton oxidativestressincreasesexpressionandactivityofbaceinnt2neurons |
| _version_ |
1724212149246492672 |
| spelling |
doaj-9f2bf446cb9a48cfb665296275e4ef512021-03-20T04:47:58ZengElsevierNeurobiology of Disease1095-953X2002-08-01103279288Oxidative Stress Increases Expression and Activity of BACE in NT2 NeuronsElena Tamagno0Paola Bardini1Alessandra Obbili2Antonella Vitali3Roberta Borghi4Damiano Zaccheo5Maria A. Pronzato6Oliviero Danni7Mark A. Smith8George Perry9Massimo Tabaton10Department 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioDepartment 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, OhioRecently 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.http://www.sciencedirect.com/science/article/pii/S0969996102905152BACEAlzheimer's diseaseHNENT2 neuronsoxidative stress |