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PMID: 17643134 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors.

British journal of pharmacology ·Vol. 153 ·No. 1 ·2008-01-00 ·Pages 6-20

Negre-Salvayre A, Coatrieux C, Ingueneau C, Salvayre R

Abstract

Reactive carbonyl compounds (RCCs) formed during lipid peroxidation and sugar glycoxidation, namely Advanced lipid peroxidation end products (ALEs) and Advanced Glycation end products (AGEs), accumulate with ageing and oxidative stress-related diseases, such as atherosclerosis, diabetes or neurodegenerative diseases. RCCs induce the 'carbonyl stress' characterized by the formation of adducts and cross-links on proteins, which progressively leads to impaired protein function and damages in all tissues, and pathological consequences including cell dysfunction, inflammatory response and apoptosis. The prevention of carbonyl stress involves the use of free radical scavengers and antioxidants that prevent the generation of lipid peroxidation products, but are inefficient on pre-formed RCCs. Conversely, carbonyl scavengers prevent carbonyl stress by inhibiting the formation of protein cross-links. While a large variety of AGE inhibitors has been developed, only few carbonyl scavengers have been tested on ALE-mediated effects. This review summarizes the signalling properties of ALEs and ALE-precursors, their role in the pathogenesis of oxidative stress-associated diseases, and the different agents efficient in neutralizing ALEs effects in vitro and in vivo. The generation of drugs sharing both antioxidant and carbonyl scavenger properties represents a new therapeutic challenge in the treatment of carbonyl stress-associated diseases.

MeSH Terms
Aging/metabolism Aldehydes/toxicity Animals Antioxidants/pharmacology Cardiovascular Diseases/etiology Cell Cycle/drug effects Humans Inflammation/etiology Lipid Peroxidation Lipoproteins, LDL/metabolism NF-kappa B/metabolism Neoplasms/etiology Neurodegenerative Diseases/etiology Oxidation-Reduction Proteins/metabolism Signal Transduction
Chemicals
Aldehydes Antioxidants Lipoproteins, LDL NF-kappa B Proteins 4-hydroxy-2-nonenal
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Negre-Salvayre A
INSERM U858, IFR-31 and Biochemistry Department, CHU Rangueil, University Toulouse-3, Toulouse, France. [email protected]
Coatrieux C
Ingueneau C
Salvayre R
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0707395
Email
[email protected]
Published
2008-01-00
Epub
2007-00-23
Pages
6-20
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2199390
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.bjp.0707395 PMC Full Text View journal details
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