Masayoshi Takeuchi1, Toshikazu Saito. 1. Department of Pathophysiological Science, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan. m-takeuchi@hokuriku-u.ac.jp
Abstract
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.
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 diabeticpatients, 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.
Authors: David Nutt; Alexandra Hayes; Leon Fonville; Rayyan Zafar; Emily O C Palmer; Louise Paterson; Anne Lingford-Hughes Journal: Nutrients Date: 2021-11-04 Impact factor: 5.717