title: Polyamine modification by acrolein exclusively produces 1,5-diazacyclooctanes: a previously unrecognized mechanism for acrolein-mediated oxidative stress.
abstract: Acrolein, a toxic unsaturated aldehyde generated as a result of oxidative stress, readily reacts with a variety of nucleophilic biomolecules. Polyamines, which produced acrolein in the presence of amine oxidase, were then found to react with acrolein to produce 1,5-diazacyclooctane, a previously unrecognized but significant downstream product of oxidative stress. Although diazacyclooctane formation effectively neutralized acrolein toxicity, the diazacyclooctane hydrogel produced through a sequential diazacyclooctane polymerization reaction was highly cytotoxic. This study suggests that diazacyclooctane formation is involved in the mechanism underlying acrolein-mediated oxidative stress.
authors.affiliation: Biofunctional Synthetic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. kotzenori@riken.jp.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Tsutsui
authors.forename: Rie
authors.initials: R
authors.lastname: Imamaki
authors.forename: Shinobu
authors.initials: S
authors.lastname: Kitazume
authors.forename: Shinya
authors.initials: S
authors.lastname: Hanashima
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Masato
authors.initials: M
authors.lastname: Kaneda
authors.forename: Shinya
authors.initials: S
authors.lastname: Oishi
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Fujii
authors.forename: Almira
authors.initials: A
authors.lastname: Kurbangalieva
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Katsunori
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000171:Acrolein / Q000378:metabolism / Q000633:toxicity*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D001392:Azocines / Q000378:metabolism / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D006146:Guanidines / Q000494:pharmacology; D006367:HeLa Cells; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D058105:Polymerization; D013095:Spermidine / Q000737:chemistry / Q000378:metabolism*; D013096:Spermine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001392:Azocines; D004791:Enzyme Inhibitors; D006146:Guanidines; D020100:Hydrogels; D013096:Spermine; D000171:Acrolein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D006631:Amine Oxidase (Copper-Containing); C004479:pimagedine; D013095:Spermidine