Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 37, Issue 7, Pages 937-945Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2004.06.012
Keywords
4-hydroxynonenal; lipid peroxidation; metabolism; protein modification; signaling; free radicals
Funding
- NIAAA NIH HHS [R01 AA09300] Funding Source: Medline
- NIEHS NIH HHS [F32 ES11937, R01 ES09410] Funding Source: Medline
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Peroxidative degradation of lipids yields the aldehyde 4-hydroxy-2-nonenal (4HNE) as a major product. The lipid aldehyde is an electrophile, and reactivity of 4HNE toward protein nucleophiles (i.e., Cys, His, and Lys) has been characterized. Through the use of purified enzymes and isolated cells, various pathways for biotransformation of the lipid aldehyde have been identified and include enzyme-mediated oxidation, reduction, and glutathione conjugation. Uncontrolled oxidative stress can yield excessive lipid peroxidation and 4FNE generation, however, and overwhelm these cellular defenses. Indeed, in vitro and in vivo production of 4HNE in response to pro-oxidant exposure has been demonstrated using antibodies to protein adducts of the lipid aldehyde. Recent evidence suggests a role for protein modification by 4HNE in the pathogenesis of several diseases (e.g., alcohol-induced liver disease); however, the precise mechanism(s) is currently unknown but likely results from adduction of proteins involved in cellular homeostasis or biological signaling. (C) 2004 Elsevier Inc. All rights reserved.
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