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 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.
Bruckner
Shane R
SR
Department of Physiology, Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
Perry
George
G
Estus
Steven
S
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007106:Immune Sera / Q000494:pharmacology; D008845:Microinjections; D019255:NADPH Oxidases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000172:deficiency / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology
D000447:Aldehydes; D007106:Immune Sera; D011506:Proteins; D017382:Reactive Oxygen Species; D020932:Nerve Growth Factor; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal