Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia.
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK.
Biomolecules. 2021 Mar 17;11(3):453. doi: 10.3390/biom11030453.
Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.
非酶糖化和蛋白质的共价修饰导致晚期糖基化终产物（AGEs）。AGEs 是衰老和神经退行性疾病的生物标志物，可由受损的神经元信号诱导。本研究的目的是研究使用模型蛋白牛血清白蛋白（BSA）在体外和使用模型生物 在体内操纵多巴胺（DA）是否会影响荧光 AGEs（fAGEs）的形成，作为多巴胺诱导的氧化事件的指标。DA 抑制了体外 fAGEs-BSA 的合成，表明具有抗氧化作用，而当苍蝇喂食 DA 时则没有观察到这种作用。喂食苍蝇可卡因和冰毒导致 fAGEs 形成增加。缺乏多巴胺转运体或 D1 型的突变体进一步升高了 fAGEs 的积累，表明 DA 功能的长期干扰会导致更高水平的 fAGEs 产生。为了证实 DA 在体内具有氧化特性，我们将抗氧化剂槲皮素（QUE）与冰毒一起喂食苍蝇。QUE 显著降低了冰毒诱导的 fAGEs 形成，表明体内 DA 功能的干扰会导致氧化增加。这些发现为使用 fAGEs 作为与 DA 相关的神经退行性变化的生物标志物以及评估 QUE 等抗氧化干预措施提供了依据。
