title: Neurotoxicity of acetaldehyde-derived advanced glycation end products for cultured cortical neurons.
abstract: 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.
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Science, Hokuriku University, Kanazawa, Japan. m-takeuchi@hokuriku-u.ac.jp
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Watai
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Sasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Choei
authors.forename: Mina
authors.initials: M
authors.lastname: Iwaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Inagaki
authors.forename: Sho-Ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Peter
authors.initials: P
authors.lastname: Riederer
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Saito
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kameda
mesh_terms: 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
chemical_list: D000418:Albumins; D000906:Antibodies; D017127:Glycation End Products, Advanced; D000079:Acetaldehyde