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
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Published in |
Journal of Neuroinflammation, May 2015
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DOI | 10.1186/s12974-015-0304-x |
Pubmed ID | |
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 |
Abstract |
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). 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. 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. 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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Finland | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 2% |
India | 1 | 2% |
Unknown | 41 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 8 | 19% |
Researcher | 6 | 14% |
Student > Doctoral Student | 4 | 9% |
Student > Bachelor | 4 | 9% |
Student > Master | 3 | 7% |
Other | 6 | 14% |
Unknown | 12 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 8 | 19% |
Biochemistry, Genetics and Molecular Biology | 6 | 14% |
Agricultural and Biological Sciences | 6 | 14% |
Medicine and Dentistry | 6 | 14% |
Engineering | 2 | 5% |
Other | 3 | 7% |
Unknown | 12 | 28% |