Amyloid β peptide-induced inhibition of endothelial nitric oxide production involves oxidative stress-mediated constitutive eNOS/HSP90 interaction and disruption of agonist-mediated Akt activation
| Autor: | Tiziana Persichini, Marco Colasanti, Manuela Bartoli, Richard C. Venema, AnnaMaria Maraschi, Carolina Muscoli, Valeria Mazzone, Michael Brennan Harris, Folami Lamoke, Micaela Gliozzi, Vincenzo Mollace |
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| Přispěvatelé: | Lamoke, Folami, Mazzone, Valeria, Persichini, Tiziana, Maraschi, Annamaria, Harris, Michael Brennan, Venema, Richard C, Colasanti, Marco, Gliozzi, Micaela, Muscoli, Carolina, Bartoli, Manuela, Mollace, Vincenzo |
| Rok vydání: | 2015 |
| Předmět: |
Vascular Endothelial Growth Factor A
Nitric Oxide Synthase Type III Immunology Pharmacology Nitric Oxide Bioinformatics medicine.disease_cause Nitric oxide Cellular and Molecular Neuroscience chemistry.chemical_compound Enos Heat shock protein Serine Animals Immunoprecipitation Medicine Drug Interactions HSP90 Heat-Shock Proteins Phosphorylation Protein kinase B Cells Cultured Amyloid beta-Peptides Dose-Response Relationship Drug biology business.industry Research General Neuroscience Endothelial Cells Free Radical Scavengers biology.organism_classification Hsp90 Acetylcysteine Vascular endothelial growth factor Oxidative Stress Neurology chemistry biology.protein Cattle Endothelium Vascular business Proto-Oncogene Proteins c-akt Oxidative stress Signal Transduction |
| Zdroj: | Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| Popis: | Background: Amyloid beta (A beta)-induced vascular dysfunction significantly contributes to the pathogenesis of Alzheimer's disease (AD). A beta is known to impair endothelial nitric oxide synthase (eNOS) activity, thus inhibiting endothelial nitric oxide production (NO). Method: In this study, we investigated A beta-effects on heat shock protein 90 (HSP90) interaction with eNOS and Akt in cultured vascular endothelial cells and also explored the role of oxidative stress in this process. Results: Treatments of endothelial cells (EC) with A beta promoted the constitutive association of HSP90 with eNOS but abrogated agonist (vascular endothelial growth factor (VEGF))-mediated HSP90 interaction with Akt. This effect resulted in blockade of agonist-mediated phosphorylation of Akt and eNOS at serine 1179. Furthermore, A beta stimulated the production of reactive oxygen species in endothelial cells and concomitant treatments of the cells with the antioxidant N-acetyl-cysteine (NAC) prevented A beta effects in promoting HSP90/eNOS interaction and rescued agonist-mediated Akt and eNOS phosphorylation. Conclusions: The obtained data support the hypothesis that oxidative damage caused by A beta results in altered interaction of HSP90 with Akt and eNOS, therefore promoting vascular dysfunction. This mechanism, by contributing to A beta-mediated blockade of nitric oxide production, may significantly contribute to the cognitive impairment seen in AD patients. |
| Databáze: | OpenAIRE |
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