Loss of the tyrosyl radical in mouse ribonucleotide reductase by (-)-epicatechin.
The flavonoid (-)-epicatechin was previously demonstrated to interfere with tyrosine nitration by peroxynitrite [Biochem. Biophys. Res. Commun. 285 (2001) 782]. This effect was hypothesized to be based upon an interaction of epicatechin with a transiently generated tyrosyl radical. In the present study, using electron paramagnetic resonance, we demonstrate that (-)-epicatechin is capable of destabilizing the tyrosyl radical of the mouse ribonucleotide reductase R2 component. First-order rate constants for the disappearance of tyrosyl radical signals were 1 x 10(-4) and 2 x 10(-4)s(-1)for epicatechin and hydroxyurea, a well-known tyrosyl radical scavenger, respectively. In keeping with scavenging the ribonucleotide reductase tyrosyl radical, cellular production of deoxyribonucleotides and DNA synthesis were impaired by (-)-epicatechin in normal human keratinocytes and in human squamous carcinoma cells.
Schroeder
Peter
P
Institut für Biochemie und Molekularbiologie I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany.
Voevodskaya
Nina
N
Klotz
Lars-Oliver
LO
Brenneisen
Peter
P
Gräslund
Astrid
A
Sies
Helmut
H
D000818:Animals; D002392:Catechin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004578:Electron Spin Resonance Spectroscopy; D051379:Mice; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D019384:Nucleic Acid Synthesis Inhibitors; D014443:Tyrosine; D002392:Catechin; D004247:DNA; D012264:Ribonucleotide Reductases