The polyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors: a new role for old molecules?
Due to the importance of glycation in the genesis of diabetic complications, an intense search for synthetic new antiglycation agents is ongoing. However, a somewhat neglected avenue is the search for endogenous compounds that may inhibit the process and be a source of protodrugs. Based on their ubiquity, their polycationic nature, their essential role in growth, their relatively high concentrations in tissues, and their high concentrations in sperm, we hypothesized that polyamines inhibit glycation and that might be one of their so far elusive functions. In this study we demonstrate a potent antiglycation effect of physiological concentrations of the polyamines spermine and spermidine. We employed two approaches: in the first, we monitored structural changes on histones and ubiquitin in which polyamines inhibit glycation-induced dimer and polymer formation. In the second we monitored functional impairment of catalytic activity of antithrombin III and plasminogen. Protection is afforded against glycation by hexoses, trioses and dicarbonyls AGE precursors and is comparable to those of aminoguanidine and carnosine.
Gugliucci
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Biochemistry Laboratory, Division of Basic Medical Sciences, Touro University, College of Osteopathic Medicine, 1310 Johnson Lane, Mare Island, Vallejo, CA 94592, USA. agugliuc@touro.edu
Menini
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D000818:Animals; D000990:Antithrombin III / Q000187:drug effects; D002336:Carnosine / Q000494:pharmacology; D002417:Cattle; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004591:Electrophoresis, Polyacrylamide Gel; D005952:Glucose-6-Phosphatase / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000032:analysis; D005985:Glyceraldehyde / Q000494:pharmacology; D006657:Histones / Q000032:analysis / Q000187:drug effects; D006801:Humans; D010958:Plasminogen / Q000187:drug effects; D011765:Pyruvaldehyde / Q000494:pharmacology; D013095:Spermidine / Q000494:pharmacology*; D013096:Spermine / Q000494:pharmacology*; D025801:Ubiquitin / Q000187:drug effects
D004338:Drug Combinations; D017127:Glycation End Products, Advanced; D006657:Histones; D025801:Ubiquitin; D013096:Spermine; D005985:Glyceraldehyde; D011765:Pyruvaldehyde; D002336:Carnosine; D000990:Antithrombin III; D010958:Plasminogen; D005952:Glucose-6-Phosphatase; D013095:Spermidine