Cytotoxicity of acetaldehyde-derived advanced glycation end-products (AA-AGE) in alcoholic-induced neuronal degeneration.
BACKGROUND
The Maillard reaction that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging and in neurodegenerative processes. We hypothesize that acetaldehyde (AA), one of the main metabolites of alcohol, may be involved in alcohol-induced neurotoxicity in vivo by formation of AA-derived AGEs (AA-AGE) with brain proteins.


METHODS
AA-AGE-bovine serum albumin (BSA) and AA-AGE-rabbit serum albumin (RSA) were prepared as described previously. Antibody specific for AA-AGE was isolated from rabbit antiserum by affinity chromatography. Primary cortical neuronal cell cultures were prepared as described previously.


RESULTS
Incubation of cortical neurons with AA-AGE produced a dose-dependent increase in neuronal cell-death, and the neurotoxicity of AA-AGE was neutralized by the addition of an anti-AA-AGE specific antibody, but not by anti-N-ethyllysine (NEL) antibody. The AA-AGE epitope was detected in human brain of alcoholism.


CONCLUSIONS
We propose that the structural epitope AA-AGE is an important toxic moiety for neuronal cells in alcoholism.
Takeuchi
Masayoshi
M
Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. m-takeuchi@hokuriku-u.ac.jp
Saito
Toshikazu
T
D000079:Acetaldehyde / Q000378:metabolism*; D000437:Alcoholism / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000032:analysis; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000166:cytology; D002846:Chromatography, Affinity; D000939:Epitopes; D000431:Ethanol / Q000633:toxicity*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000031:analogs & derivatives / Q000276:immunology; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects; D051381:Rats
D000906:Antibodies; D002492:Central Nervous System Depressants; D000939:Epitopes; D017127:Glycation End Products, Advanced; C117804:ethyl lysine; D000431:Ethanol; D000079:Acetaldehyde; D008239:Lysine