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

Carla R. García, Carlos Angelé-Martínez, Jenna A. Wilkes, Hsiao-Chuan Wang, Erin E. Battin, Julia L. Brumaghim

Research output: Contribution to journalArticle

22 Citations (Scopus)

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 (IC 50 values of 3.2 to 18 μM) and are electrochemically active. However, glycine and glutamate are more effective at preventing copper-mediated DNA damage (IC 50 values of 35 and 12.9 μM, respectively) than l-DOPA, the only catecholamine to prevent this damage (IC 50 = 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 Fe 3+ over Fe 2+ and Cu 2+ 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.

Original languageEnglish (US)
Pages (from-to)6458-6467
Number of pages10
JournalDalton Transactions
Volume41
Issue number21
DOIs
StatePublished - Jun 7 2012
Externally publishedYes

Fingerprint

Dihydroxyphenylalanine
Curcumin
Catecholamines
Neurotransmitter Agents
Copper
Iron
Antioxidants
Metals
Amino Acids
DNA
Glycine
Glutamic Acid
Aminobutyrates
Oxidation
Epinephrine
Cyclic voltammetry
Metal ions
Dopamine
Norepinephrine
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Inorganic Chemistry

Cite this

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. / García, Carla R.; Angelé-Martínez, Carlos; Wilkes, Jenna A.; Wang, Hsiao-Chuan; Battin, Erin E.; Brumaghim, Julia L.

In: Dalton Transactions, Vol. 41, No. 21, 07.06.2012, p. 6458-6467.

Research output: Contribution to journalArticle

García, Carla R. ; Angelé-Martínez, Carlos ; Wilkes, Jenna A. ; Wang, Hsiao-Chuan ; Battin, Erin E. ; Brumaghim, Julia L. / 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. In: Dalton Transactions. 2012 ; Vol. 41, No. 21. pp. 6458-6467.
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