通过抑制ISG15/NOX4轴相关的氧化应激,DRD4可缓解急性损伤
Yue Gao1, Xun Lu1, Guangyuan Zhang1
1Surgical Research Center, Institute of Urology, Medical School of Southeast University, Nanjing, China; Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, China.
Redox biology
|February 14, 2024
概括
多巴胺D4受体 (DRD4) 通过降低氧化应激和细胞死亡来防止急性损伤 (AKI). 这一发现提供了一个潜在的新治疗策略,用于由缺血症/再输液或西斯素引起的损伤.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 急性损伤 (AKI) 呈现出显著的发病率和死亡率,临床预测和治疗选择有限.
- 氧化应激和线粒体功能障碍是AKI病变发生的关键因素.
- 多巴胺D4受体 (DRD4) 与氧化应激途径有关.
研究的目的:
- 研究DRD4对急性损伤的保护作用.
- 阐明DRD4可能减轻毒性的机制.
主要方法:
- 在体内研究使用小鼠模型的缺血/反损伤 (IRI) 和西斯诱导的毒性.
- 在体外实验中,HK-2细胞接受过低氧/低氧化或西斯的实验.
- 转录组测序以识别下游目标和分子途径.
主要成果:
- 在IRI或西斯治疗后,脏中的DRD4表达显著降低.
- 通过抑制活性氧物种 (ROS) 和NADPH氧化酶4 (NOX4) 表达,增强线粒体功能,DRD4的使用减轻了毒性.
- DRD4保护了HK-2细胞免受氧化应激诱导的亡.
- 从机理上讲,DRD4降低了ISG15的调节,导致NOX4的ISGylation减少,NOX4无处不在的增加,以及随后的降解.
结论:
- DRD4对IRI和西斯胺诱导的AKI都有显著的保护作用.
- DRD4通过减轻氧化应激和亡作用,部分通过ISG15-NOX4通路.
- 对于预防和治疗急性损伤来说,DRD4是一个有前途的治疗标.
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