Effects of hypoxia and oxidative stress on expression of neprilysin in human neuroblastoma cells and rat cortical neurones and astrocytes.
Pathogenesis of Alzheimer's disease (AD), which is characterised by accumulation of extracellular deposits of beta-amyloid peptide (Abeta) in the brain, has recently been linked to vascular disorders such as ischemia and stroke. Abeta is constantly produced in the brain from amyloid precursor protein (APP) through its cleavage by beta- and gamma-secretases and certain Abeta species are toxic for neurones. The brain has an endogenous mechanism of Abeta removal via proteolytic degradation and the zinc metalloproteinase neprilysin (NEP) is a critical regulator of Abeta concentration. Down-regulation of NEP could predispose to AD. By comparing the effects of hypoxia and oxidative stress on expression and activity of the Abeta-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.
Fisk
Lilia
L
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Mount Preston Street, Leeds, LS2 9JT, UK.
Nalivaeva
Natalia N
NN
Boyle
John P
JP
Peers
Christopher S
CS
Turner
Anthony J
AJ
D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002908:Chronic Disease; D005470:Fluorometry; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D002534:Hypoxia, Brain / Q000378:metabolism*; D015260:Neprilysin / Q000096:biosynthesis*; D009447:Neuroblastoma / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D053764:Presenilin-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016564:Amyloid beta-Protein Precursor; D051272:Glucose Transporter Type 1; D053764:Presenilin-1; D012333:RNA, Messenger; D006861:Hydrogen Peroxide; D015260:Neprilysin