Intense oxidative DNA damage promoted by l‐DOPA and its metabolites implications for neurodegenerative disease

FEBS Letters

Aruoma, Okezie I.¹  Kaur, Harparkash¹  Lees, Andrew J.²  Jenner, Peter¹  Evans, Patricia J.¹  Jenner, Andrew¹  Halliwell, Barry¹  Dexter, David T.¹  Spencer, Jeremy P.E.¹  Marsden, David C.² 

[1] Neurodegenerative Disease Research Centre, Pharmacology Group, King's College, Manresa Road, London SW3 6LX, UK;Parkinson's Disease Society, Brain Bank, Institute of Neurology, Queen Square, London WC1N 3BG, UK

关键词: DNA damage;    Copper;    l-DOPA;    Hydroxyl radical;    Parkinson's disease;    5-OH uracil;    5;    hydroxyuracil;    5-OH;    Me Uracil;    5-(hydroxymethyl)uracil;    FapyAdenine;    4;    6-diamino-5-formamido pyrimidine;    OH Ade;    8-hydroxyadenine;    FapyGuanine;    2;    6-diamino-4-hydroxy-5 formamidopyrimidine;    8-OH guanine;    8-hydroxyguanine;   

DOI  :  10.1016/0014-5793(94)01056-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxidative DNA damage can cause mutation and cell death. We show that l-DOPA, dopamine and 3-O-methyl-DOPA cause extensive oxidative DNA damage in the presence of H₂O₂ and traces of copper ions. 8-Hydroxyguanine is the major product. Iron ions were much less effective and manganese ions did not catalyse DNA damage. We propose that copper ion release, in the presence of l-DOPA and its metabolites, may be an important mechanism of neurotoxicity, e.g. in Parkinson's disease and amyotrophic lateral sclerosis.

【 授权许可】

Unknown