Cited by 551Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

Amyloid β-Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation

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Mark, Robert J., Pang, Zhen, Geddes, James W., Uchida, Koji, Mattson, Mark P.·1997·The Journal of Neuroscience

Abstract

A deficit in glucose uptake and a deposition of amyloid β-peptide (Aβ) each occur in vulnerable brain regions in Alzheimer’s disease (AD). It is not known whether mechanistic links exist between Aβ deposition and impaired glucose transport. We now report that Aβ impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation. Aβ impaired 3 H-deoxy-glucose transport in a concentration-dependent manner and with a time course preceding neurodegeneration. The decrease in glucose transport was followed by a decrease in cellular ATP levels. Impairment of glucose transport, ATP depletion, and cell death were each prevented in cultures pretreated with antioxidants. Exposure to FeSO 4, an established inducer of lipid peroxidation, also impaired glucose transport. Immunoprecipitation and Western blot analyses showed that exposure of cultures to Aβ induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced a concentration-dependent impairment of glucose transport and subsequent ATP depletion. Impaired glucose transport was not caused by a decreased energy demand in the neurons, because ouabain, which inhibits Na+/K+-ATPase activity and thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose transport. Collectively, the data demonstrate that lipid peroxidation mediates Aβ-induced impairment of glucose transport in neurons and suggest that this action of Aβ may contribute to decreased glucose uptake and neuronal degeneration in AD.

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Crossref · 10.1523/jneurosci.17-03-01046.1997

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  1. Mark RJ, Lovell MA, Markesbery WR, Uchida K, Mattson MP (1997) A role for 4-hydroxynonenal in disruption of ion homeostasis and neuro- nal death induced by amyloid ␤-peptide. J Neurochem, in press.

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Authors
Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., & Mattson, M. P.
Affiliations
University of Kentucky (US)
Venue
The Journal of Neuroscience
Published
1997-02-01
Volume
17
Issue
3
Pages
1046-1054
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1830456158
Cited by
551
References
74
Citations by year
2026: 3 · 2025: 9 · 2024: 4 · 2023: 13 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 10 · 2018: 11 · 2017: 15 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 19 · 2012: 13
FWCI
20.19
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Alzheimer's Association (AG05144)
  • National Institutes of Health (5r01ns030583-04, AG05144)
  • National Institute on Aging (P50AG005144, AG-05144, P01AG010836, AG 10836)
  • National Institute of Neurological Disorders and Stroke (NS30583)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, glucose transport, lipid peroxidation, GLUT3, 4-hydroxynonenal, Alzheimer's disease, hippocampal neurons, cortical neurons, ATP depletion, oxidative stress, antioxidants, neurodegeneration, Na+/K+-ATPase
MeSH terms
Adenosine Triphosphate, Aldehydes, Animals, Biological Transport, Cells, Cultured, Cerebral Cortex, Glucose, Hippocampus, Lipid Peroxidation, Amyloid beta-Peptides, Oxidative Stress, Rats

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