4‐Hydroxynonenal contributes to NGF withdrawal‐induced neuronal apoptosis

Reactive oxygen species are a necessary triggering event for apoptosis of sympathetic neurons after nerve growth factor (NGF) withdrawal. Reactive oxygen species can lead to the generation of 4‐hydroxynonenal (HNE), a highly reactive aldehyde that forms adducts with proteins. This covalent modificat...

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Bibliographic Details
Published in:Journal of neurochemistry 2003-05, Vol.85 (4), p.999-1005
Main Authors: Bruckner, Shane R., Perry, George, Estus, Steven
Format: Article
Language:English
Subjects:
4-Hydroxynonenal
Ageing, cell death
Aldehydes - metabolism
Animals
apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
Cell physiology
Cells, Cultured
Fundamental and applied biological sciences. Psychology
Immune Sera - pharmacology
Microinjections
Molecular and cellular biology
NADPH Oxidases - metabolism
Nerve Growth Factor - deficiency
Nerve Growth Factor - pharmacology
Neurons - cytology
Neurons - drug effects
Neurons - metabolism
NGF withdrawal
oxidative stress
Proteins - metabolism
Rats
Reactive Oxygen Species - metabolism
Second Messenger Systems - physiology
Signal Transduction - drug effects
Signal Transduction - physiology
Sympathetic Nervous System - cytology
sympathetic neuron
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Summary:Reactive oxygen species are a necessary triggering event for apoptosis of sympathetic neurons after nerve growth factor (NGF) withdrawal. Reactive oxygen species can lead to the generation of 4‐hydroxynonenal (HNE), a highly reactive aldehyde that forms adducts with proteins. This covalent modification can activate or inhibit signal transduction pathways involved in the induction of apoptosis. This process may be clinically relevant because HNE‐adduct immunoreactivity increases in several disease states. Here we evaluate the role of HNE‐adducts in sympathetic neurons undergoing NGF‐deprivation‐induced apoptosis, a model of developmental programmed cell death. We show that HNE‐adduct immunoreactivity is dramatically increased after NGF‐withdrawal in an NADPH oxidase‐dependent manner. Moreover, HNE‐adducts appear to contribute to NGF‐deprivation‐induced apoptotic signal transduction because microinjected HNE‐adduct antiserum protects sympathetic neurons from NGF withdrawal. In conclusion, this report suggests the direct contribution of endogenously generated HNE in the stimulation of apoptotic signal transduction in neurons.
ISSN:0022-3042
1471-4159
DOI:10.1046/j.1471-4159.2003.01749.x