Neurochemical Research

, Volume 32, Issue 10, pp 1741–1748

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

  • Lilia Fisk
  • Natalia N. Nalivaeva
  • John P. Boyle
  • Christopher S. Peers
  • Anthony J. Turner
Original Paper

DOI: 10.1007/s11064-007-9349-2

Cite this article as:
Fisk, L., Nalivaeva, N.N., Boyle, J.P. et al. Neurochem Res (2007) 32: 1741. doi:10.1007/s11064-007-9349-2

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.

Keywords

Human neuroblastoma NB7 cells Aβ-degrading enzymes Neprilysin Hypoxia Oxidative stress Primary cortical neurones Astrocytes Alzheimer’s disease 

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

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Lilia Fisk
    • 1
  • Natalia N. Nalivaeva
    • 1
  • John P. Boyle
    • 2
  • Christopher S. Peers
    • 2
  • Anthony J. Turner
    • 1
  1. 1.Institute of Molecular and Cellular Biology, Faculty of Biological SciencesUniversity of LeedsLeedsUK
  2. 2.AU Cardiovascular MedicineUniversity of LeedsLeedsUK