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Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes

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Abstract

Pathogenesis of Alzheimer’s disease (AD), which is characterised by accumulation of extracellular deposits of β-amyloid peptide (Aβ) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Aβ is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by β- and γ-secretases and certain Aβ species are toxic for neurones. The brain has an endogenous mechanism of Aβ removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Aβ concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Aβ-degrading enzyme NEP in human neuroblastoma NB7 cells and rat primary cortical neurones we have demonstrated that hypoxia reduced NEP expression at the protein and mRNA levels as well as its activity. On contrary in astrocytes hypoxia increased NEP mRNA expression.

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Abbreviations

AD:

Alzheimer’s disease

NEP:

Neprilysin

ECE:

Endothelin converting enzyme

IDE:

Insulin degrading enzyme

APP:

Amyloid precursor protein

GLUT1:

Glucose transporter 1

PS1:

Presenilin 1

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Acknowledgements

This work was supported by Medical Research Council, UK and The Biochemical Society (Mrs L Fisk).

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Authors and Affiliations

  1. Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Mount Preston Street, Leeds, LS2 9JT, UK

    Lilia Fisk, Natalia N. Nalivaeva & Anthony J. Turner

  2. AU Cardiovascular Medicine, University of Leeds, Leeds, LS2 9JT, UK

    John P. Boyle & Christopher S. Peers

Authors
  1. Lilia Fisk
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  2. Natalia N. Nalivaeva
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  3. John P. Boyle
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  4. Christopher S. Peers
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  5. Anthony J. Turner
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Correspondence to Natalia N. Nalivaeva.

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Special issue dedicated to Dr. Moussa Youdim.

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Fisk, L., Nalivaeva, N.N., Boyle, J.P. et al. Effects of Hypoxia and Oxidative Stress on Expression of Neprilysin in Human Neuroblastoma Cells and Rat Cortical Neurones and Astrocytes. Neurochem Res 32, 1741–1748 (2007). https://doi.org/10.1007/s11064-007-9349-2

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  • DOI: https://doi.org/10.1007/s11064-007-9349-2

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