Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan.
Int J Mol Sci. 2024 Oct 10;25(20):10880. doi: 10.3390/ijms252010880.
Advanced glycation end products (AGEs) with multiple structures are formed at the sites where carbonyl groups of reducing sugars bind to free amino groups of proteins through the Maillard reaction. In recent years, it has been highlighted that the accumulation of AGEs, which are generated when carbonyl compounds produced in the process of sugar metabolism react with proteins, is involved in various diseases. Creatine is a biocomponent that is homeostatically present throughout the body and is known to react nonenzymatically with α-dicarbonyl compounds. This study evaluated the antiglycation potential of creatine against methylglyoxal (MGO), a glucose metabolite that induces carbonyl stress with formation of AGEs in vitro. Further, to elucidate the mechanism of the cytoprotective action of creatine, its effect on the accumulation of carbonyl proteins in the cells and the MGO-induced cellular damage were investigated using neuroblastoma cells. The results revealed that creatine significantly inhibits protein carbonylation by directly reacting with MGO, and creatine added to the culture medium suppressed MGO-derived carbonylation of intracellular proteins and exerted a protective effect on MGO-induced cytotoxicity. These findings suggest that endogenous and supplemented creatine may contribute to the attenuation of carbonyl stress in vivo.
高级糖基化终产物（AGEs）具有多种结构，是在还原糖的羰基与蛋白质的游离氨基通过美拉德反应结合的部位形成的。近年来，人们强调指出，当糖代谢过程中产生的羰基化合物与蛋白质反应时，生成的 AGEs 的积累与各种疾病有关。肌酸是一种生物成分，在体内保持着内稳态，并且已知其可与α-二羰基化合物非酶促反应。本研究评估了肌酸对甲基乙二醛（MGO）的抗糖化潜力，MGO 是一种葡萄糖代谢物，可在体外诱导羰基应激，形成 AGEs。此外，为了阐明肌酸的细胞保护作用机制，使用神经母细胞瘤细胞研究了肌酸对细胞内羰基蛋白积累和 MGO 诱导的细胞损伤的影响。结果表明，肌酸通过与 MGO 直接反应显著抑制蛋白质羰基化，添加到培养基中的肌酸抑制了细胞内蛋白质的 MGO 衍生羰基化，并对 MGO 诱导的细胞毒性具有保护作用。这些发现表明，内源性和补充的肌酸可能有助于减轻体内的羰基应激。
