Different mechanisms between copper and iron in catecholamines-mediated oxidative DNA damage and disruption of gene expression in vitro
| Autor: | Yoshihiko Nishino, Yoshinori Okamoto, Rena Makino, Motozumi Ando, Nakao Kojima, Koji Ueda |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Nitrilotriacetic Acid
DNA damage Catechols Gene Expression Oxidative phosphorylation In Vitro Techniques Toxicology Ferric Compounds chemistry.chemical_compound Catecholamines Dopamine Gene expression medicine Animals Gene chemistry.chemical_classification Reactive oxygen species General Neuroscience Copper toxicity DNA medicine.disease Biochemistry chemistry Lac Operon Cattle Reactive Oxygen Species Oxidation-Reduction Copper medicine.drug DNA Damage |
| Zdroj: | Neurotoxicity research. 20(1) |
| ISSN: | 1476-3524 |
| Popis: | Catechols produce reactive oxygen species (ROS) and induce oxidative DNA damage through reduction–oxidation reactions with metals such as copper. Here, we examined oxidative DNA damage by neurotransmitter catecholamines in the presence of copper or iron and evaluated the effects of this damage on gene expression in vitro. Dopamine induced strand breaks and base oxidation in calf thymus DNA in the presence of Cu(II) or Fe(III)-NTA (nitrilotriacetic acid). The extent of this damage was greater for Cu(II) than for Fe(III)-NTA. For the DNA damage induced by dopamine, the responsible reactive species were hydrogen peroxide and Cu(I) for Cu(II) and hydroxyl radicals and Fe(II) for Fe(III)-NTA. Cu(II) induced DNA conformational changes, but Fe(III)-NTA did not in the presence of dopamine. These differences indicate different modes of action between Cu and Fe-NTA with regard to the induction of DNA damage. Expression of the lacZ gene coded on plasmid DNA was inhibited depending on the extent of the oxidative damage and strand breaks. Endogenous catecholamines (dopamine, adrenaline, and noradrenaline) were more potent than catechols (no aminoalkyl side chains) or 3,4-dihydroxybenzylamine (aminomethyl side chain). These results suggest that the metal-mediated DNA damage induced by dopamine disrupts gene expression, and leukoaminochromes (further oxidation products of O-quinones having aminoethyl side chain) are involved in the DNA damage. These findings indicate a possibility that metal (especially iron and copper)-mediated oxidation of catecholamines plays an important role in the pathogenesis of neurodegenerative disorders including Parkinson’s disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink