Neurotoxicity of acetaldehyde-derived advanced glycation end products for cultured cortical neurons.
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-AGEs) with brain proteins. 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. We propose that the structural epitope AA-AGE is an important toxic moiety for neuronal cells in alcoholism.
Takeuchi
Masayoshi
M
Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan. m-takeuchi@hokuriku-u.ac.jp
Watai
Takayuki
T
Sasaki
Nobuyuki
N
Choei
Hiroshi
H
Iwaki
Mina
M
Ashizawa
Takeshi
T
Inagaki
Yosuke
Y
Yamagishi
Sho-Ichi
S
Kikuchi
Seiji
S
Riederer
Peter
P
Saito
Toshikazu
T
Bucala
Richard
R
Kameda
Yukihiko
Y
D000079:Acetaldehyde / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D000418:Albumins / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology; D002417:Cattle; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D000418:Albumins; D000906:Antibodies; D017127:Glycation End Products, Advanced; D000079:Acetaldehyde