Biochemistry Department, Faculty of Sciences, Ege University, 35100, Bornova, Izmir, Turkey.
Central Research Test and Analysis Laboratory Application and Research Center, Ege University, 35100, Bornova, Izmir, Turkey.
Biometals. 2020 Dec;33(6):353-364. doi: 10.1007/s10534-020-00254-0. Epub 2020 Sep 30.
Age-related complications including protein alterations seen in diabetes and Alzheimer's disease are a major issue due to their accumulation and deleterious effects. This report aims to investigate the effect of zinc supplementation on the anti-glycoxidation activity of carnosine on the in vitro model of albumin-based protein modification. Besides, the therapeutic effect of this combination was tested through the addition of the molecules in tandem (co-treatment) or post initiation (post-treatment) of the protein modification process. Glycation was induced via the addition of glucose to which carnosine (5 mM) alone or with various zinc concentrations (125, 250, and 500 μM) were added either at 0 h or 24 h post-glycation induction. On the other hand, protein oxidation was induced using chloramine T (20 mM) and treated in the same way with carnosine and zinc. The different markers of glycation (advanced glycation end products (AGEs), dityrosine, and beta-sheet formation (aggregation)) and oxidation (AOPP, advanced oxidation protein products) were estimated via fluorescence and colorimetric assays. Zinc addition induced a significant enhancement of carnosine activity by reducing albumin modification that outperformed aminoguanidine both in the co- and post-treatment protocols. Zinc demonstrated a supplementary effect in combination with carnosine highlighting its potential in the protection against age-related protein modifications processes such as the ones found in diabetes.
由于其积累和有害作用,与年龄相关的并发症,包括糖尿病和阿尔茨海默病中所见的蛋白质改变,是一个主要问题。本报告旨在研究锌补充对肌肽抗糖基化活性的影响,以体外白蛋白蛋白修饰模型为基础。此外,通过添加分子(联合治疗)或在蛋白质修饰过程开始后(后处理)来测试这种组合的治疗效果。通过向其中添加葡萄糖来诱导糖化,单独添加肌肽(5 mM)或添加不同浓度的锌(125、250 和 500 μM),在糖化诱导后 0 小时或 24 小时添加。另一方面,使用氯胺 T(20 mM)诱导蛋白质氧化,并以相同方式用肌肽和锌处理。通过荧光和比色测定法评估不同的糖化标记物(晚期糖基化终产物(AGEs)、二酪氨酸和β-折叠形成(聚集))和氧化标记物(AOPP,晚期氧化蛋白产物)。锌的添加通过减少白蛋白修饰显著增强了肌肽的活性,在联合和后处理方案中,其效果均优于氨基胍。锌与肌肽联合具有补充作用,突出了其在预防与年龄相关的蛋白质修饰过程中的潜力,如糖尿病中发现的那些过程。