- Koji Ueda (Faculty of Pharmacy, Meijo University / email@example.com)
Faculty of Pharmacy, Meijo University
Oxidative stress is involved in the development of many neurological diseases. The interactions between catecholamines and copper or iron generate reactive oxygen species that lead to oxidative DNA damage in vitro. Furthermore, catechol structure is essential for DNA damage. Here, we clarified the effect of aminoethyl side chains on DNA damage. Endogenous catecholamines (dopamine, noradrenaline, and adrenaline) were more effective than other catechols (catechol, 4-ethylcatechol, and 3,4-dihydroxybenzylamine) in strand break and base oxidation of calf thymus DNA. The presence of copper caused more DNA damage than iron. Furthermore, adrenaline oxidized to adrenochrome more rapidly by copper than iron. Leukoadrenochrome, an oxidation intermediate formed by the intramolecular cyclization of aminoethyl side chains, rapidly increased the formation of 8-hydroxy-2′-deoxyguanosine compared with adrenalin. These results show the effect of aminoethyl side chains in catecholamine-induced oxidative DNA damage. This mechanism may partly show the vulnerability of catecholaminergic neurons against oxidative stress.