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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2015

Open Access 01-12-2015 | Research

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

Authors: Folami Lamoke, Valeria Mazzone, Tiziana Persichini, Annamaria Maraschi, Michael Brennan Harris, Richard C Venema, Marco Colasanti, Micaela Gliozzi, Carolina Muscoli, Manuela Bartoli, Vincenzo Mollace

Published in: Journal of Neuroinflammation | Issue 1/2015

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Abstract

Background

Amyloid β (Aβ)-induced vascular dysfunction significantly contributes to the pathogenesis of Alzheimer’s disease (AD). Aβ is known to impair endothelial nitric oxide synthase (eNOS) activity, thus inhibiting endothelial nitric oxide production (NO).

Method

In this study, we investigated Aβ-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 Aβ 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, Aβ stimulated the production of reactive oxygen species in endothelial cells and concomitant treatments of the cells with the antioxidant N-acetyl-cysteine (NAC) prevented Aβ 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 Aβ results in altered interaction of HSP90 with Akt and eNOS, therefore promoting vascular dysfunction. This mechanism, by contributing to Aβ-mediated blockade of nitric oxide production, may significantly contribute to the cognitive impairment seen in AD patients.
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Metadata
Title
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
Authors
Folami Lamoke
Valeria Mazzone
Tiziana Persichini
Annamaria Maraschi
Michael Brennan Harris
Richard C Venema
Marco Colasanti
Micaela Gliozzi
Carolina Muscoli
Manuela Bartoli
Vincenzo Mollace
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2015
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-015-0304-x

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