Metal-catalyzed oxidation of 2-alkenals generates genotoxic 4-oxo-2-alkenals during lipid peroxidation. Issue 10 (2nd October 2016)

• Record Type: Journal Article
• Authors: Nuka, Erika; Tomono, Susumu; Ishisaka, Akari; Kato, Yoji; Miyoshi, Noriyuki; Kawai, Yoshichika
• Is Part Of: Bioscience, biotechnology, and biochemistry. Volume 80:Issue 10(2016)
• Page Start: 2007
• Page End: 2013
• Publication Date: 2016-10-02
• Subjects: lipid peroxidation -- DNA adducts -- LC-MS/MS -- 4-oxo-2-alkenals -- transition metals; Biotechnology -- Periodicals; Biochemistry -- Periodicals; 660.6
• DOI: 10.1080/09168451.2016.1191334
• Languages: English
• ISSNs: 0916-8451

Abstract

Abstract: Lipid peroxidation products react with cellular molecules, such as DNA bases, to form covalent adducts, which are associated with aging and disease processes. Since lipid peroxidation is a complex process and occurs in multiple stages, there might be yet unknown reaction pathways. Here, we analyzed comprehensively 2′-deoxyguanosine (dG) adducts with oxidized arachidonic acid using liquid chromatography–tandem mass spectrometry and found the formation of 7-(2-oxo-hexyl)-etheno-dG as one of the major unidentified adducts. The formation of this adduct was reproduced in the reaction of dG with 2-octenal and predominantly with 4-oxo-2-octenal (OOE). We also found that other 2-alkenals (with five or more carbons) generate corresponding 4-oxo-2-alkenal-type adducts. Importantly, it was found that transition metals enhanced the oxidation of C4-position of 2-octenal, leading to the formation of OOE-dG adduct. These findings demonstrated a new pathway for the formation of 4-oxo-2-alkenals during lipid peroxidation and might provide a mechanism for metal-catalyzed genotoxicity. Graphical abstract: : 4-Oxo-2-alkenals, which are highly reactive to nucleosides, are generated through metal-catalyzed oxidation of corresponding 2-alkenals during lipid peroxidation.