College of Pharmacy, Gachon University, #191, Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
Gachon Institute of Pharmaceutical Science, Gachon University, #191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Korea.
Cells. 2020 Jan 17;9(1):234. doi: 10.3390/cells9010234.
Methylglyoxal (MGO), a highly reactive dicarbonyl compound, is a key precursor of the formation of advanced glycation end products (AGEs). MGO and MGO-AGEs were reportedly increased in patients with diabetic dysfunction, including diabetic nephropathy. The activation of glyoxalase-I (GLO-I) increases MGO and MGO-AGE detoxification. MGO-mediated glucotoxicity can also be ameliorated by MGO scavengers such as -acetylcysteine (NAC), aminoguanidine (AG), and metformin. In this study, we noted that l-cysteine demonstrated protective effects against MGO-induced glucotoxicity in renal mesangial cells. l-cysteine prevented MGO-induced apoptosis and necrosis, together with a reduction of reactive oxygen species (ROS) production in MES13 cells. Interestingly, l-cysteine significantly reduced MGO-AGE formation and also acted as an MGO-AGE crosslink breaker. Furthermore, l-cysteine treatment accelerated MGO catabolism to D-lactate via the upregulation of GLO-I. The reduction of AGE formation and induction of AGE breakdown, following l-cysteine treatment, further supports the potential use of l-cysteine as an alternative for the therapeutic control of MGO-induced renal complications in diabetes, especially against diabetic nephropathy.
甲基乙二醛（MGO）是一种高度反应性的二羰基化合物，是形成晚期糖基化终产物（AGEs）的关键前体。据报道，糖尿病功能障碍患者，包括糖尿病肾病患者的 MGO 和 MGO-AGE 水平升高。糖基化酶-I（GLO-I）的激活可增加 MGO 和 MGO-AGE 的解毒作用。MGO 介导的糖毒性也可以通过 MGO 清除剂如 -乙酰半胱氨酸（NAC）、氨基胍（AG）和二甲双胍来缓解。在这项研究中，我们注意到 l-半胱氨酸对 MGO 诱导的肾小球系膜细胞糖毒性具有保护作用。l-半胱氨酸可预防 MGO 诱导的细胞凋亡和坏死，并减少 MES13 细胞中活性氧（ROS）的产生。有趣的是，l-半胱氨酸可显著减少 MGO-AGE 的形成，并且可作为 MGO-AGE 的交联断裂剂。此外，l-半胱氨酸处理通过上调 GLO-I 加速 MGO 向 D-乳酸的代谢。l-半胱氨酸处理后 AGE 形成减少和 AGE 分解诱导进一步支持 l-半胱氨酸作为治疗糖尿病中 MGO 诱导的肾脏并发症的替代物的潜力，特别是针对糖尿病肾病。
