title: Immunochemical crossreactivity of antibodies specific for "advanced glycation endproducts" with "advanced lipoxidation endproducts".
abstract: Antibodies against advanced glycation endproducts (AGEs) are used for their immunohistological localization in tissues, for example in Alzheimer's disease (AD) or diabetes. Many monoclonal and polyclonal antibodies have been used, and their specificity is unknown in most cases. Increased radical production, leading to the formation of lipid-derived reactive carbonyl species, such as malondialdehyde (MDA), acrolein, and glyoxal, is a characteristic aspect of age-related diseases like Alzheimer's disease or diabetic polyneuropathy. These reactive carbonyl species are able to modify proteins, resulting in AGE related structures, termed "advanced lipoxidation products" (ALEs). In this study, the monoclonal carboxymethyllysine-specific antibody 4G9 and the polyclonal AGE-antibody K2189 were tested for their immunoreactivity towards these carbonyl-derived protein modifications. To investigate which carbonyl-modified amino acid side chains are specifically recognized by these antibodies, peptide membranes were incubated with glyoxal, MDA and acrolein. As model proteins, microtubuli associated protein tau (MAP-tau), beta-amyloid, human serum albumin and chicken egg albumin were incubated likewise. It was found that both antibodies detected reaction products of these carbonyl compounds on lysine- and arginine residues and for the protein modification, it was found that some epitopes might not be detected. In conclusion, AGE-antibodies might not only detect sugar-derived AGEs but also structures derived from lipid peroxidation products (serving as markers of oxidative stress).
authors.affiliation: Neuroimmunological Cell Biology Unit, Interdisciplinary Center of Clinical Research (IZKF), Leipzig, Germany.
authors.forename: Torsten
authors.initials: T
authors.lastname: Richter
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Lüth
authors.forename: Thomas
authors.initials: T
authors.lastname: Arendt
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Kientsch-Engel
authors.forename: Peter
authors.initials: P
authors.lastname: Stahl
authors.forename: Dörte
authors.initials: D
authors.lastname: Fengler
authors.forename: Björn
authors.initials: B
authors.lastname: Kuhla
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D000596:Amino Acids / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D001921:Brain / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry; D002645:Chickens; D005260:Female; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D015151:Immunoblotting / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D015227:Lipid Peroxidation / Q000276:immunology*; D008297:Male; D010063:Ovum; D016875:tau Proteins / Q000378:metabolism
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D000906:Antibodies; D015415:Biomarkers; D002241:Carbohydrates; D017127:Glycation End Products, Advanced; D016875:tau Proteins