Neurochemical Research

, Volume 31, Issue 4, pp 523–532

Mechanism of DNA Damage and Apoptosis Induced by Tetrahydropapaveroline, a Metabolite of Dopamine

Authors

  • Hatasu Kobayashi
    • Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine
    • Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine
    • Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine
  • Shosuke Kawanishi
    • Department of Environmental and Molecular Medicine Mie University Graduate School of Medicine
Article

DOI: 10.1007/s11064-006-9044-8

Cite this article as:
Kobayashi, H., Oikawa, S. & Kawanishi, S. Neurochem Res (2006) 31: 523. doi:10.1007/s11064-006-9044-8

Abstract

Tetrahydropapaveroline (THP), a metabolite of dopamine, has been suspected to be associated with dopaminergic neurotoxicity of L-DOPA. THP induced apoptosis in human leukemia cell line HL-60 cells, but did not in its hydrogen peroxide (H2O2)-resistant clone HP100. THP-induced DNA ladder formation in HL-60 cells was inhibited by a metal chelator. THP induced damage to 32P-labeled DNA fragments in the presence of metals. In the presence of Fe(III)EDTA, THP caused DNA damage at every nucleotide. The DNA damage was inhibited by free hydroxy radical (·OH) scavengers and catalase, suggesting that the Fe(III)EDTA-mediated DNA damage is mainly due to ·OH generation. In the presence of Cu(II), THP caused DNA damage mainly at T and G of 5′-TG-3′ sequence. The inhibitive effect of catalase and bathocuproine on Cu(II)-mediated DNA damage suggested that H2O2 and Cu(I) participate in the DNA damage. This study demonstrated that THP-induced apoptosis via reactive oxygen species generated from reaction of H2O2 and metals plays an important role in cytotoxicity of L-DOPA.

Keywords

TetrahydropapaverolineL-DOPADNA damageParkinson’s diseaseHydrogen peroxideMetal

Abbreviations

THP

tetrahydropapaveroline

PD

Parkinson’s disease

H2O2

hydrogen peroxide

DA

dopamine

MAO

monoamine oxidase

8-oxodG

8-oxo-7,8-dihydro-2′-deoxyguanosine

CIP

calf intestine phosphatase

DTPA

diethylenetriamine-N,N,N,N′′,N′′-pentaacetic acid

DMSO

dimethylsulfoxide

SOD

superoxide dismutase

Fpg

formamidopyrimidine-DNA glycosylase

HPLC-ECD

an electrochemical detector coupled to high-performance liquid chromatography

Copyright information

© Springer Science+Business Media, Inc. 2006