Wu Xueyan, Li Jing, Wang Shaopeng, Jiang Liping, Sun Xiance, Liu Xiaofang, Yao Xiaofeng, Zhang Cong, Wang Ningning, Yang Guang
Department of Food Nutrition and Safety, Dalian Medical University, No. 9W. Lushun South Road, Dalian 116044, China.
Department of Pathology, Dalian Medical University, Dalian 116044, China.
J Agric Food Chem. 2021 May 5;69(17):5206-5215. doi: 10.1021/acs.jafc.1c01305. Epub 2021 Apr 20.
Exposure to particulate matter has been associated with diseases of the respiratory and cardiovascular systems. Owing to the dense vasculature of the kidney, it has also been identified as a PM target organ. A potential contributor to PM-mediated damage may be the promotion of inflammation. The essential oil 2-undecanone (2-methyl nonyl ketone) is an isolate, and it has been shown to possess diverse pharmacologic effects, including anti-inflammatory properties. In this study we explored the ability of 2-undecanone to protect against PM-induced kidney inflammation and the exact mechanisms in this process. We found that PM elevated the levels of certain inflammatory cytokines in BALB/c mice and in HEK 293 cells. Supplementation with 2-undecanone attenuated this PM-induced inflammatory injury. Interestingly, in HEK 293 cells, the PM-associated inflammation was aggravated by the mitophagy inhibitor Medivi-1, while it was attenuated by rapamycin, indicating that the mechanism of 2-undecanone-mediated inhibition of inflammation may relate to mitophagy. Meanwhile, 2-undecanone induces mitophagy in HEK 293 cells by suppressing Akt1-mTOR signaling. These results indicate that PM can induce kidney inflammation, and mitophagy induced by 2-undecanone may play a protective role against this renal inflammation.
接触颗粒物与呼吸系统和心血管系统疾病有关。由于肾脏血管密集，它也被确定为颗粒物的靶器官。颗粒物介导的损伤的一个潜在促成因素可能是炎症的加剧。香精油2-十一烷酮（2-甲基壬基酮）是一种分离物，已显示具有多种药理作用，包括抗炎特性。在本研究中，我们探讨了2-十一烷酮预防颗粒物诱导的肾脏炎症的能力以及这一过程中的具体机制。我们发现，颗粒物会提高BALB/c小鼠和HEK 293细胞中某些炎性细胞因子的水平。补充2-十一烷酮可减轻这种颗粒物诱导的炎性损伤。有趣的是，在HEK 293细胞中，线粒体自噬抑制剂Medivi-1会加剧与颗粒物相关的炎症，而雷帕霉素则可减轻炎症，这表明2-十一烷酮介导的炎症抑制机制可能与线粒体自噬有关。同时，2-十一烷酮通过抑制Akt1-mTOR信号传导在HEK 293细胞中诱导线粒体自噬。这些结果表明，颗粒物可诱导肾脏炎症，而2-十一烷酮诱导的线粒体自噬可能对这种肾脏炎症起到保护作用。
