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Cited by 580Cell death mechanisms and regulationAntioxidant Activity and Oxidative StressRedox biology and oxidative stress

Cell death and diseases related to oxidative stress: 4-hydroxynonenal (HNE) in the balance

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Dalleau, S, Baradat, M, Guéraud, F, Huc, L·2013·Cell Death & Differentiation
DOI 10.1038/cdd.2013.138PMC PMC3824598
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Abstract

During the last three decades, 4-hydroxy-2-nonenal (HNE), a major α,β-unsaturated aldehyde product of n-6 fatty acid oxidation, has been shown to be involved in a great number of pathologies such as metabolic diseases, neurodegenerative diseases and cancers. These multiple pathologies can be explained by the fact that HNE is a potent modulator of numerous cell processes such as oxidative stress signaling, cell proliferation, transformation or cell death. The main objective of this review is to focus on the different aspects of HNE-induced cell death, with a particular emphasis on apoptosis. HNE is a special apoptotic inducer because of its abilities to form protein adducts and to propagate oxidative stress. It can stimulate intrinsic and extrinsic apoptotic pathways and interact with typical actors such as tumor protein 53, JNK, Fas or mitochondrial regulators. At the same time, due to its oxidant status, it can also induce some cellular defense mechanisms against oxidative stress, thus being involved in its own detoxification. These processes in turn limit the apoptotic potential of HNE. These dualities can imbalance cell fate, either toward cell death or toward survival, depending on the cell type, the metabolic state and the ability to detoxify.

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  • Brains of Alzheimer's disease patients have high levels of cerebrospinal fluid 4-HNE and increased 4-HNE adducts on neurofilaments and amyloid β plaques.

    “Indeed, the brains of Alzheimer’s disease patients have high levels of cerebrospinal fluid 4-HNE and increased 4-HNE adducts on neurofilaments and amyloid β plaques [57].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [57]

    The “Neurodegenerative diseases” passage in the HNE and Diseases Associated with Oxidative Damage section reports HNE adducts to neurofilaments and high HNE levels in amyloid β plaques and cerebrospinal fluid in Alzheimer’s patients. It does not say that HNE adducts on the plaques themselves are increased. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • 4-HNE can reach levels as high as 1 μM in normal human plasma; concentrations as high as 100 μM have been observed near the site of lipid peroxidation.

    “4-HNE can reach levels as high as 1 µM in normal human plasma [72]; however, concentrations as high as 100 µM have been observed near the site of lipid peroxidation [57].”

    From Rlip76: An Unexplored Player in Neurodegeneration and Alzheimer’s Disease? (2022) · cites this paper as [57]

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Authors
Dalleau, S., Baradat, M., Guéraud, F., & Huc, L.
Affiliations
Université Toulouse III - Paul Sabatier (FR)
Corresponding author
Huc, L
ORCID
Venue
Cell Death & Differentiation
Publisher
Springer Science and Business Media LLC
Published
2013-10-04
Volume
20
Issue
12
Pages
1615-1630
ISSN
  • 1350-9047 (ISSN-L)
  • 1476-5403
DOI
10.1038/cdd.2013.138
PMC
PMC3824598
OpenAlex
W2024519961
Cited by
580
References
8
Citations by year
2026: 45 · 2025: 62 · 2024: 62 · 2023: 64 · 2022: 65 · 2021: 64 · 2020: 44 · 2019: 33 · 2018: 29 · 2017: 36 · 2016: 35 · 2015: 25 · 2014: 13 · 2013: 2 · 2012: 1
FWCI
2.35
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Cell Death and Differentiation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Funders
  • Agence Nationale de la Recherche
  • Institut National Du Cancer
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
4-hydroxynonenal, lipid peroxidation, oxidative stress, apoptosis, cell death, protein adducts, α,β-unsaturated aldehydes, mitochondrial apoptosis, extrinsic apoptotic pathway, p53, JNK, Fas, detoxification, neurodegenerative diseases, cancer, metabolic disorders
MeSH terms
Aldehydes, Animals, Disease, Humans, Lipid Peroxidation, Signal Transduction, Cell Death, Oxidative Stress

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