Wang Wenping, Wu Ximing, Yang Chung S, Zhang Jinsong
State Key Laboratory of Tea Plant Biology and Utilization, School of Tea & Food Science, Anhui Agricultural University, Hefei 230036, China.
Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Antioxidants (Basel). 2021 Sep 30;10(10):1564. doi: 10.3390/antiox10101564.
Neurotransmitter catecholamines (dopamine, epinephrine, and norepinephrine) are liable to undergo oxidation, which copper is deeply involved in. Catecholamine oxidation-derived neurotoxicity is recognized as a pivotal pathological mechanism in neurodegenerative diseases. Glutamate, as an excitatory neurotransmitter, is enriched in the brain at extremely high concentrations. However, the chemical biology relationship of these two classes of neurotransmitters remains largely unknown. In the present study, we assessed the influences of glutamate on the autoxidation of catecholamines, the copper- and copper-containing ceruloplasmin-mediated oxidation of catecholamines, the catecholamine-induced formation of quinoprotein, catecholamine/copper-induced hydroxyl radicals, and DNA damage in vitro. The results demonstrate that glutamate, at a physiologically achievable molar ratio of glutamate/catecholamines, has a pronounced inhibitory effect on catecholamine oxidation, catecholamine oxidation-evoked hydroxyl radicals, quinoprotein, and DNA damage. The protective mechanism of glutamate against catecholamine oxidation could be attributed to its restriction of the redox activity of copper via chelation. This previously unrecognized link between glutamate, catecholamines, and copper suggests that neurodegenerative disorders may occur and develop once the built-in equilibrium is disrupted and brings new insight into developing more effective prevention and treatment strategies for neurodegenerative diseases.
神经递质儿茶酚胺（多巴胺、肾上腺素和去甲肾上腺素）易于发生氧化，铜在其中起着重要作用。儿茶酚胺氧化衍生的神经毒性被认为是神经退行性疾病的关键病理机制。谷氨酸作为一种兴奋性神经递质，在大脑中以极高的浓度富集。然而，这两类神经递质之间的化学生物学关系在很大程度上仍然未知。在本研究中，我们评估了谷氨酸对儿茶酚胺自氧化、铜和含铜铜蓝蛋白介导的儿茶酚胺氧化、儿茶酚胺诱导的醌蛋白形成、儿茶酚胺/铜诱导的羟基自由基以及体外DNA损伤的影响。结果表明，在生理可达到的谷氨酸/儿茶酚胺摩尔比下，谷氨酸对儿茶酚胺氧化、儿茶酚胺氧化诱发的羟基自由基、醌蛋白和DNA损伤具有显著的抑制作用。谷氨酸对儿茶酚胺氧化的保护机制可能归因于其通过螯合作用限制了铜的氧化还原活性。这种谷氨酸、儿茶酚胺和铜之间以前未被认识到的联系表明，一旦内在平衡被打破，神经退行性疾病可能会发生和发展，这为开发更有效的神经退行性疾病预防和治疗策略带来了新见解。
