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

Hong, Jie-Ru; Zhang, Chen-Yu; Zhong, Wen-Jing; Yang, Hui-Hui; Xiong, Jian‑Bing; Deng, Ping; Yang, Nan-Shi-Yu; Chen, Hui; Jin, Ling; Guan, Cha-Xiang; Duan, Jia-Xi; Zhou, Yong

doi:10.1016/j.biopha.2023.115937

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…Furthermore, to assess whether the effects of AOSs were specifically mediated by Nrf2, we employed a specific Nrf2 inhibitor known as ML385 [52]. This inhibitor affects the transcriptional activity of Nrf2 and has been utilized to elucidate the involvement of the Nrf2 pathway in the mechanism of action of various substances [53][54][55][56][57]. Our findings indicate that ML385 affected the cell viability of GES-1 treated with AOS and exposed to peroxide, increasing intracellular ROS levels and affecting the expression protein levels of Nrf2 and HO-1.…”

Section: Discussionmentioning

confidence: 99%

Alginate Oligosaccharides Protect Gastric Epithelial Cells against Oxidative Stress Damage through Induction of the Nrf2 Pathway

Acevedo,

Covarrubias,

Haeger

et al. 2024

Antioxidants

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Gastric diseases represent a significant global public health challenge, characterized by molecular dysregulation in redox homeostasis and heightened oxidative stress. Although prior preclinical studies have demonstrated the cytoprotective antioxidant effects of alginate oligosaccharides (AOSs) through the Nrf2 pathway, whether such mechanisms apply to gastric diseases remains unclear. In this study, we used the GES-1 gastric cell line exposed to hydrogen peroxide (H2O2) as a damage model to investigate the impact of AOS on cell viability and its associated mechanisms. Our results revealed that pre-incubation with AOS for either 4 h or 24 h significantly improved the viability of GES-1 cells exposed to H2O2. In addition, AOS reduced the intracellular ROS levels, activating the Nrf2 signaling pathway, with increased Nrf2 protein and mRNA expression and a significant upregulation of the target genes HO-1 and NQO1. The activation of Nrf2 was correlated with decreased Keap1 protein expression and an increased level of the autophagy protein p62/SQSTM1, suggesting the activation of Nrf2 through a noncanonical pathway. This study suggests that AOS is a potential treatment for protecting gastric epithelial cells from oxidative stress by activating the p62/SQSTM1-Keap1-Nrf2 axis and laying the foundation for future investigations about its specific therapeutic mechanisms.

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