N1-acetyl-N2-formyl-5-methoxykynuramine, a biogenic amine and melatonin metabolite, functions as a potent antioxidant.
The biogenic amine The biogenic amine N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) was investigated for its potential antioxidative capacity. AFMK is a metabolite generated through either an enzymatic or a chemical reaction pathway from melatonin. The physiological function of AFMK remains unknown. To our knowledge, this report is the first to document the potent antioxidant action of this biogenic amine. Cyclic voltammetry (CV) shows that AFMK donates two electrons at potentials of 456 mV and 668 mV, and therefore it functions as a reductive force. This function contrasts with all other physiological antioxidants that donate a single electron only when they neutralize free radicals. AFMK reduced 8-hydroxydeoxyguanosine formation induced by the incubation of DNA with oxidants significantly. Lipid peroxidation resulting from free radical damage to rat liver homogenates was also prevented by the addition of AFMK. The inhibitory effects of AFMK on both DNA and lipid damage appear to be dose-response related. In cell culture, AFMK efficiently reduced hippocampal neuronal death induced by either hydrogen peroxide, glutamate, or amyloid b25-35 peptide. AFMK is a naturally occurring molecule with potent free radical scavenging capacity (donating two electrons/molecule) and thus may be a valuable new antioxidant for preventing and treating free radical-related disorders.
Tan
D X
DX
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Manchester
L C
LC
Burkhardt
S
S
Sainz
R M
RM
Mayo
J C
JC
Kohen
R
R
Shohami
E
E
Huo
Y S
YS
Hardeland
R
R
Reiter
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death; D002478:Cells, Cultured; D002614:Chelating Agents; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D005296:Ferrous Compounds / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007735:Kynuramine / Q000031:analogs & derivatives / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008550:Melatonin / Q000378:metabolism; D019216:Metals, Heavy / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D002614:Chelating Agents; D005296:Ferrous Compounds; D005609:Free Radicals; D019216:Metals, Heavy; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D007735:Kynuramine; D018698:Glutamic Acid; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D008550:Melatonin