Lv Tingting, Lu Yao, Liu Yi, Feng Hong, Li Chensheng, Sheng Wei, Cui Zhengguo, Zhu Suwei, Gu Xia, Yang Zhe, Wan Qiang
School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Department of Pulmonary and Critical Care Medicine, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Oxid Med Cell Longev. 2021 Feb 17;2021:6691226. doi: 10.1155/2021/6691226. eCollection 2021.
Diabetic kidney disease (DKD) is the major cause of end-stage renal disease (ESRD). In the past few decades, there has been a large amount of evidence to highlight the pivotal role of oxidative stress in the development and progression of DKD. However, the detailed molecular mechanisms are not fully elucidated. A new sight has been established that the mitochondrial acetyltransferase GCN5L1 participates in cellular redox homeostasis maintenance in DKD. Firstly, we found that the expression of GCN5L1 is significantly elevated both in human and mouse kidney tissues with DKD and in hyperglycemic renal tubular epithelial cells (TECs), while deletion of GCN5L1 could effectively ameliorate oxidative stress-induced renal injury in DKD. Furthermore, deletion of GCN5L1 could reduce MnSOD acetylation on lysine 68 and activate its activity, thereby scavenging excessive ROS and relieving oxidative stress-induced renal inflammation and fibrosis. In general, GCN5L1-mediated acetylation of MnSOD exacerbated oxidative stress-induced renal injury, suggesting that GCN5L1 might be a potential intervention target in DKD.
糖尿病肾病（DKD）是终末期肾病（ESRD）的主要病因。在过去几十年中，大量证据凸显了氧化应激在DKD发生发展过程中的关键作用。然而，其详细的分子机制尚未完全阐明。一种新的观点认为，线粒体乙酰转移酶GCN5L1参与了DKD中细胞氧化还原稳态的维持。首先，我们发现GCN5L1在患有DKD的人和小鼠肾脏组织以及高血糖肾小管上皮细胞（TECs）中的表达均显著升高，而敲除GCN5L1可有效改善氧化应激诱导的DKD肾损伤。此外，敲除GCN5L1可减少锰超氧化物歧化酶（MnSOD）赖氨酸68位点的乙酰化并激活其活性，从而清除过量的活性氧（ROS）并减轻氧化应激诱导的肾炎症和纤维化。总体而言，GCN5L1介导的MnSOD乙酰化加剧了氧化应激诱导的肾损伤，这表明GCN5L1可能是DKD的一个潜在干预靶点。
