2. Academic Validation
  3. Epoxyeicosatrienoic acids alleviate alveolar epithelial cell senescence by inhibiting mitophagy through NOX4/Nrf2 pathway

Epoxyeicosatrienoic acids alleviate alveolar epithelial cell senescence by inhibiting mitophagy through NOX4/Nrf2 pathway

  • Biomed Pharmacother. 2023 Nov 24:169:115937. doi: 10.1016/j.biopha.2023.115937.
Jie-Ru Hong 1,  Chen-Yu Zhang 2,  Wen-Jing Zhong 2,  Hui-Hui Yang 2,  Jian-Bing Xiong 3,  Ping Deng 2,  Nan-Shi-Yu Yang 2,  Hui Chen 2,  Ling Jin 2,  Cha-Xiang Guan 2,  Jia-Xi Duan 4,  Yong Zhou 5
Affiliations

Affiliations

  • 1 Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, Hunan 410078, China.
  • 2 Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, Hunan 410078, China.
  • 3 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China.
  • 4 Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410078, China. Electronic address: [email protected].
  • 5 Department of Physiology, School of Basic Medicine Science, Central South University, Changsha, Hunan 410078, China. Electronic address: [email protected].
PMID: 38007934 DOI: 10.1016/j.biopha.2023.115937
Abstract

Alveolar epithelial cell (AEC) senescence is considered to be a universal pathological feature of many chronic pulmonary diseases. Our previous study found that epoxyeicosatrienoic acids (EETs), produced from arachidonic acid (ARA) through the Cytochrome P450 cyclooxygenase (CYP) pathway, have significant negative regulatory effects on cellular senescence in AECs. However, the exact mechanisms by which EETs alleviate the senescence of AECs still need to be further explored. In the present study, we observed that bleomycin (BLM) induced enhanced Mitophagy accompanied by increased mitochondrial ROS (mito-ROS) content in the murine alveolar epithelial cell line MLE12. While EETs reduced BLM-induced Mitophagy and mito-ROS content in MLE12 cells, and the mechanism was related to the regulation of NOX4/Nrf2-mediated redox imbalance. Furthermore, we found that inhibition of EETs degradation could significantly inhibit Mitophagy and regulate NOX4/Nrf2 balance to exert anti-oxidant effects in D-galactose-induced premature aging mice. Collectively, these findings may provide new ideas for treating age-related pulmonary diseases by targeting EETs to improve mitochondrial dysfunction and reduce oxidative stress.

Keywords

Alveolar epithelial cell; Epoxyeicosatrienoic acids; Mitophagy; NOX4; Nrf2; Senescence.

Figures
Products