科研之友
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摘要
Oxidative stress contributes to the progression of neurodegenerative diseases and considerable attention has been given to the development of new antioxidant-based therapies aimed at limiting neuronal cell damage. Structural analysis of catecholamine neurotransmitters indicates that these molecules can exhibit antioxidant activity due to the presence of a catechol moiety. This hypothesis is confirmed in cell culture experiments but the mechanism of antioxidant action of catecholamines is not described. Herein, we present quantitative kinetic studies on the effect of dopamine (DA) and L-3,4-dihydroxyphenylalanine (L-DOPA) on the peroxidation of methyl linoleate dispersed in Triton X-100 micelles as a model heterogeneous lipid system. Experiments were performed at extended pH range 4.0-10.0 in order to study how protonation/deprotonation of catecholamine affect its antioxidant activity. At pH 4.0-7.0, the activity of catecholamines is limited to retardation of lipid peroxidation (caused by the reaction of catecholamines with initiating radicals in the aqueous phase). The effective suppression of lipid peroxidation can be achieved by applying catecholamines together with an analogue of alpha-tocopherol (2,2,5,7,8-pentamethyl-6-hydroxychroman, PMHC). For example, a mixture of 1 mu M PMHC with 10 mu M L-DOPA causes 18-fold elongation of suppression time as compared to 1 mu M PMHC used alone. We suggest that catecholamines together with alpha-tocopherol efficiently enhance the protection of biological systems from oxidative stress. At pH above 8.0 a prooxidative effect caused by reaction of semiquinone radical anions with molecular oxygen is observed. However, this toxic action can be completely suppressed by PMHC acting as an agent removing the potentially harmful semiquinone radicals from the reaction environment.
- 出版日期2015-6
