大黄素
活性氧
抗氧化剂
细胞凋亡
谷胱甘肽
程序性细胞死亡
GPX4
药理学
氧化应激
癌症研究
化学
医学
细胞生物学
谷胱甘肽过氧化物酶
生物
生物化学
酶
超氧化物歧化酶
作者
Jing Ji,Pengyu Tao,Qian Wang,Mengmeng Cui,Mingfeng Cao,Yuzhen Xu
出处
期刊:Aging
[Impact Journals, LLC]
日期:2023-08-07
被引量:2
标识
DOI:10.18632/aging.204933
摘要
Diabetic kidney disease (DKD) poses a threat to people's health. The current treatments only provide partial relief of symptoms. Therefore, seeking a promising therapeutic medication for the prevention and control on DKD will benefit patients. Recently, a novel iron-dependent and non-apoptotic regulated mode of cell death, termed as ferroptosis, is expected to offer us a novel insight into the mechanism of DKD. We conducted experiments to investigate the role of ferroptosis in the development of DKD. Iron accumulation, weakened antioxidant capacity and ROS overproduction were observed in the renal tissues of STZ-induced diabetic rats. A persistent high glucose condition contributed to down regulated levels of Glutathione Peroxidase 4 (GPX4) and Solute Carrier Family 7 Member 11 (SLC7A11) which marked the occurrence of ferroptosis. Treatment of Emodin in DKD models could significantly attenuated these changes and reduced renal injury. Besides, NFE2-related factor 2 (Nrf2), an important antioxidant regulator, was inhibited in both in vivo and in vitro assay, which contributes to Reactive Oxygen Species (ROS) generation that further promoted the expression of ferroptosis related protein. These unwanted effects were offset by the intervention of Emodin. The specific Nrf2 knock out enhanced cell's sensitivity to ferroptosis by being exposed to high glucose culture, which was improved by treatment of Emodin via restoring activity of Nrf2. In conclusion, our research demonstrated that Emodin exerted renal protection against DKD via inhibiting ferroptosis and restoring Nrf2 mediated antioxidant capacity, which could be employed as a novel therapeutic medication against DKD.
科研通智能强力驱动
Strongly Powered by AbleSci AI