4-hydroxynonenal increases neuronal susceptibility to oxidative stress
Article first published online: 12 JAN 2000
Copyright © 1999 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 58, Issue 6, pages 823–830, 15 December 1999
How to Cite
Keller, J. N., Hanni, K. B. and Markesbery, W. R. (1999), 4-hydroxynonenal increases neuronal susceptibility to oxidative stress. J. Neurosci. Res., 58: 823–830. doi: 10.1002/(SICI)1097-4547(19991215)58:6<823::AID-JNR9>3.0.CO;2-T
- Issue published online: 12 JAN 2000
- Article first published online: 12 JAN 2000
- Manuscript Accepted: 13 AUG 1999
- Manuscript Revised: 10 AUG 1999
- Manuscript Received: 30 APR 1999
- Abercrombie Foundation (W.R.M.)
- The Kleberg Foundation (W.R.M.)
- National Institutes of Health. Grant Number: 1-PO1-AG05119, W.R.M.
- The John Douglas French Foundation/American Heart Association (J.N.K.)
- lipid peroxidation;
- reactive oxygen species
Increased levels of reactive oxygen species occur in neurodegenerative disorders and may promote neuron death. The lipid peroxidation product 4-hydroxynonenal (HNE) is increased in neurons following oxidative stress and promotes neuron death in vitro and in vivo. The present study examined the possibility that HNE can increase neuron vulnerability to oxidative stress. Application of low concentrations of HNE (50–500 nM) increased neuron death induced by β-amyloid or glutamate when added within 3 hr of injury. In addition, treatment with HNE exacerbated mitochondrial reactive oxygen species formation and loss of mitochondrial membrane potential in response to β-amyloid and glutamate. The ability to exacerbate oxidative stress, mitochondrial dysfunction, and neuron death appears to be specific to HNE, because application of other lipid peroxidation products had no effect. These data indicate a role for low levels of HNE in promoting reactive oxygen species accumulation and neuron degeneration by altering mitochondrial homeostasis. In addition, the present study indicates a possible mechanism for reactive oxygen species and lipid peroxidation toxicity in neurodegenerative conditions. J. Neurosci. Res. 58:823–830, 1999. © 1999 Wiley-Liss, Inc.