Jump to main content
Jump to site search

Issue 21, 2012
Previous Article Next Article

Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism

Author affiliations

Abstract

Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates. In contrast to amino acid neurotransmitters, catecholamine neurotransmitters, L-DOPA, and curcumin prevent significant iron-mediated DNA damage (IC50 values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC50 values of 35 and 12.9 μM, respectively) than L-DOPA, the only catecholamine to prevent this damage (IC50 = 73 μM). This metal-mediated DNA damage prevention is directly related to the metal-binding behaviour of these compounds. When bound to iron or copper, the catecholamines, amino acids, and curcumin significantly shift iron oxidation potentials and stabilize Fe3+ over Fe2+ and Cu2+ over Cu+, a factor that may prevent metal redox cycling in vivo. These results highlight the disparate antioxidant activities of neurotransmitters, drugs, and supplements and highlight the importance of considering metal binding when identifying antioxidants to treat and prevent neurodegenerative disorders.

Graphical abstract: Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, l-DOPA, and curcumin: metal binding as a general antioxidant mechanism

Back to tab navigation

Supplementary files

Publication details

The article was received on 10 Jan 2012, accepted on 08 Mar 2012 and first published on 26 Mar 2012


Article type: Paper
DOI: 10.1039/C2DT30060E
Citation: Dalton Trans., 2012,41, 6458-6467
  •   Request permissions

    Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism

    C. R. García, C. Angelé-Martínez, J. A. Wilkes, H. C. Wang, E. E. Battin and J. L. Brumaghim, Dalton Trans., 2012, 41, 6458
    DOI: 10.1039/C2DT30060E

Search articles by author

Spotlight

Advertisements