Metal-catalyzed oxidation of 2-alkenals generates genotoxic 4-oxo-2-alkenals during lipid peroxidation.
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.
a Departmentof Food Science , Institute of Biomedical Sciences, TokushimaUniversity Graduate School , Tokushima , Japan.
Erika
E
Nuka
b Laboratory of Longevity Biochemistry, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate Program in Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
Susumu
S
Tomono
c Research Institute for Food and Nutritional Sciences , University of Hyogo , Himeji , Japan.
Akari
A
Ishisaka
c Research Institute for Food and Nutritional Sciences , University of Hyogo , Himeji , Japan.
Yoji
Y
Kato
b Laboratory of Longevity Biochemistry, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, Graduate Program in Food and Nutritional Sciences , University of Shizuoka , Shizuoka , Japan.
Noriyuki
N
Miyoshi
a Departmentof Food Science , Institute of Biomedical Sciences, TokushimaUniversity Graduate School , Tokushima , Japan.
Yoshichika
Y
Kawai
D000447:Aldehydes / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000737:chemistry*; D015227:Lipid Peroxidation; D009153:Mutagens / Q000737:chemistry* / Q000378:metabolism; D010084:Oxidation-Reduction
C506590:4-oxo-2-octenal; D000447:Aldehydes; D009153:Mutagens; D016718:Arachidonic Acid; D003300:Copper; D007501:Iron; D003849:Deoxyguanosine
4-oxo-2-alkenals; DNA adducts; LC-MS/MS; lipid peroxidation; transition metals