Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia

Webster, Nicola J.; Green, Kim N.; Peers, Chris; Vaughan, Peter F. T.

doi:10.1046/j.1471-4159.2002.01236.x

Cited by 56Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and Treatments

Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia

Webster, Nicola J., Green, Kim N., Peers, Chris, Vaughan, Peter F. T.·2002·Journal of Neurochemistry

DOI 10.1046/j.1471-4159.2002.01236.x

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Abstract

Alzheimer's disease (AD) is more prevalent following an ischemic or hypoxic episode, such as stroke. Indeed, brain levels of amyloid precursor protein (APP) and the cytotoxic amyloid beta peptide (Abeta) fragment are enhanced in these patients and in animal models following experimental ischaemia. We have investigated the effect of chronic hypoxia (CH; 2.5% O2, 24 h) on processing of APP in the human neuroblastoma, SH-SY5Y. We demonstrate that constitutive and muscarinic-receptor-enhanced secretion of the alpha-secretase cleaved fragment of APP, sAPPalpha, was reduced by approximately 60% in CH cells. The caspase inhibitor BOC-D(Ome)FMK did not reverse this effect of CH, and CH cells were as viable as controls, based on MTT assays. Thus, loss of sAPPalpha is not related to cell death or caspase processing of APP. Pre-incubation with antioxidants did not reverse the effect of CH, and the effect could not be mimicked by H2O2, discounting the involvement of reactive oxygen species in hypoxic loss of sAPPalpha. CH did not affect muscarinic activation of extracellular-signal regulated kinase. However, expression of ADAM 10 (widely believed to be alpha-secretase) was decreased approximately 50% following CH. Thus, CH selectively decreases processing of APP by the alpha-secretase pathway, most likely by decreasing levels of ADAM 10.

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Muscarine, a positive regulator of PLA2, is a potent inducer of sAPPα in human neuroblastoma SH-SY5Y cells.
“It is interesting that muscarine, a positive regulator of PLA2, is also a potent inducer of sAPPα in human neuroblastoma SH-SY5Y cells (Webster et al., 2002; Wood et al., 2000);”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Webster et al., 2002

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Authors: Webster, N. J., Green, K. N., Peers, C., & Vaughan, P. F. T.
Affiliations: University of Leeds (GB)
ORCID: Green, Kim N.
Peers, Chris
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2002-12
Volume: 83
Issue: 6
Pages: 1262-1271
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1046/j.1471-4159.2002.01236.x
OpenAlex: W1601310757
Cited by: 56
References: 51
Citations by year: 2026: 1 · 2024: 1 · 2023: 1 · 2021: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 2 · 2015: 3 · 2014: 2 · 2013: 4 · 2012: 3
FWCI: 1.60
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 10 d)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Alzheimer Society
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: amyloid precursor protein, chronic hypoxia, ADAM10, muscarinic receptors, extracellular signal-regulated kinase, reactive oxygen species, Alzheimer's disease, ischemia, SH-SY5Y cells
MeSH terms: Animals, Antioxidants, Cell Survival, Enzyme Inhibitors, Humans, Muscarine, Neuroblastoma, Peptide Fragments, Endopeptidases, Protein Processing, Post-Translational, Tumor Cells, Cultured, Blotting, Western, Cell Hypoxia, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, PC12 Cells, Oxidants, Muscarinic Agonists, Rats, Amyloid Precursor Protein Secretases, Caspase Inhibitors

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Altered processing of amyloid precursor protein in the human neuroblastoma SH-SY5Y by chronic hypoxia

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