Yongchang Chen, Yan Wu, Juan Dong, Chuanming Zhang, Jia Tang
{"title":"Acacetin通过激活NRF2/SLC7A11/GPX4信号抑制铁凋亡，减轻香烟烟雾提取物诱导的人支气管上皮细胞损伤","authors":"Yongchang Chen, Yan Wu, Juan Dong, Chuanming Zhang, Jia Tang","doi":"10.1007/s12013-024-01659-1","DOIUrl":null,"url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) stands as a major contributor to mortality worldwide, with cigarette smoke being a primary causative factor. Acacetin has been reported to possess lung protective effects. However, the precise role and mechanism of Acacetin in COPD remains elusive. In this study, human bronchial epithelial cell line HBE135-E6E7 was treated with Acacetin under cigarette smoke extract (CSE) conditions. Cellular viability was assessed using CCK-8 and LDH kits. Reactive oxygen species (ROS) generation was tested with DCFH-DA staining. JC-1 staining was employed to examine the mitochondrial membrane potential (MMP). Additionally, hydroxynonenal (4-HNE) level was tested using immunofluorescence staining and mitochondrial lipid peroxidation was evaluated using MitoPeDPP staining. MitoSOX staining was used to detect mitochondrial (mito)-ROS. Fe<sup>2+</sup> level was measured using FerroOrange staining and the expression of ferroptosis-related proteins was detected with western blot. Besides, the binding between Acacetin and NRF2 was analyzed by molecular docking. The sequent NRF2 overexpression or knockdown was used to explore the regulation of Acacetin on NRF2/SLC7A11/GPX4 signaling. Results indicated that CSE significantly reduced the viability, augmented ROS generation and decreased MMP in HBE135-E6E7 cells, which were blocked by Acacetin addition. Moreover, Acacetin inhibited lipid peroxidation and ferroptosis in CSE-treated HBE135-E6E7 cells. Specifically, Acacetin targeted NRF2 and activated the NRF2/SLC7A11/GPX4 signaling in CSE-induced HBE135-E6E7 cells. Furthermore, NRF2 deficiency or ML-385 treatment notably restored the influences of Acacetin on oxidative stress and ferroptosis in HBE135-E6E7 cells challenged with CSE. In conclusion, Acacetin alleviated CSE-induced injury in HBE135-E6E7 cells by activating The NRF2/SLC7A11/GPX4 signaling to inhibit ferroptosis.</p>","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Acacetin Attenuates Cigarette Smoke Extract-Induced Human Bronchial Epithelial Cell Injury by Activating NRF2/SLC7A11/GPX4 Signaling to Inhibit Ferroptosis.\",\"authors\":\"Yongchang Chen, Yan Wu, Juan Dong, Chuanming Zhang, Jia Tang\",\"doi\":\"10.1007/s12013-024-01659-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Chronic obstructive pulmonary disease (COPD) stands as a major contributor to mortality worldwide, with cigarette smoke being a primary causative factor. Acacetin has been reported to possess lung protective effects. However, the precise role and mechanism of Acacetin in COPD remains elusive. In this study, human bronchial epithelial cell line HBE135-E6E7 was treated with Acacetin under cigarette smoke extract (CSE) conditions. Cellular viability was assessed using CCK-8 and LDH kits. Reactive oxygen species (ROS) generation was tested with DCFH-DA staining. JC-1 staining was employed to examine the mitochondrial membrane potential (MMP). Additionally, hydroxynonenal (4-HNE) level was tested using immunofluorescence staining and mitochondrial lipid peroxidation was evaluated using MitoPeDPP staining. MitoSOX staining was used to detect mitochondrial (mito)-ROS. Fe<sup>2+</sup> level was measured using FerroOrange staining and the expression of ferroptosis-related proteins was detected with western blot. Besides, the binding between Acacetin and NRF2 was analyzed by molecular docking. The sequent NRF2 overexpression or knockdown was used to explore the regulation of Acacetin on NRF2/SLC7A11/GPX4 signaling. Results indicated that CSE significantly reduced the viability, augmented ROS generation and decreased MMP in HBE135-E6E7 cells, which were blocked by Acacetin addition. Moreover, Acacetin inhibited lipid peroxidation and ferroptosis in CSE-treated HBE135-E6E7 cells. Specifically, Acacetin targeted NRF2 and activated the NRF2/SLC7A11/GPX4 signaling in CSE-induced HBE135-E6E7 cells. Furthermore, NRF2 deficiency or ML-385 treatment notably restored the influences of Acacetin on oxidative stress and ferroptosis in HBE135-E6E7 cells challenged with CSE. In conclusion, Acacetin alleviated CSE-induced injury in HBE135-E6E7 cells by activating The NRF2/SLC7A11/GPX4 signaling to inhibit ferroptosis.</p>\",\"PeriodicalId\":510,\"journal\":{\"name\":\"Cell Biochemistry and Biophysics\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":1.8000,\"publicationDate\":\"2025-01-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Biochemistry and Biophysics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1007/s12013-024-01659-1\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biochemistry and Biophysics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12013-024-01659-1","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Acacetin Attenuates Cigarette Smoke Extract-Induced Human Bronchial Epithelial Cell Injury by Activating NRF2/SLC7A11/GPX4 Signaling to Inhibit Ferroptosis.
Chronic obstructive pulmonary disease (COPD) stands as a major contributor to mortality worldwide, with cigarette smoke being a primary causative factor. Acacetin has been reported to possess lung protective effects. However, the precise role and mechanism of Acacetin in COPD remains elusive. In this study, human bronchial epithelial cell line HBE135-E6E7 was treated with Acacetin under cigarette smoke extract (CSE) conditions. Cellular viability was assessed using CCK-8 and LDH kits. Reactive oxygen species (ROS) generation was tested with DCFH-DA staining. JC-1 staining was employed to examine the mitochondrial membrane potential (MMP). Additionally, hydroxynonenal (4-HNE) level was tested using immunofluorescence staining and mitochondrial lipid peroxidation was evaluated using MitoPeDPP staining. MitoSOX staining was used to detect mitochondrial (mito)-ROS. Fe2+ level was measured using FerroOrange staining and the expression of ferroptosis-related proteins was detected with western blot. Besides, the binding between Acacetin and NRF2 was analyzed by molecular docking. The sequent NRF2 overexpression or knockdown was used to explore the regulation of Acacetin on NRF2/SLC7A11/GPX4 signaling. Results indicated that CSE significantly reduced the viability, augmented ROS generation and decreased MMP in HBE135-E6E7 cells, which were blocked by Acacetin addition. Moreover, Acacetin inhibited lipid peroxidation and ferroptosis in CSE-treated HBE135-E6E7 cells. Specifically, Acacetin targeted NRF2 and activated the NRF2/SLC7A11/GPX4 signaling in CSE-induced HBE135-E6E7 cells. Furthermore, NRF2 deficiency or ML-385 treatment notably restored the influences of Acacetin on oxidative stress and ferroptosis in HBE135-E6E7 cells challenged with CSE. In conclusion, Acacetin alleviated CSE-induced injury in HBE135-E6E7 cells by activating The NRF2/SLC7A11/GPX4 signaling to inhibit ferroptosis.
期刊介绍：
Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems
The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized.
Examples of subject areas that CBB publishes are:
· biochemical and biophysical aspects of cell structure and function;
· interactions of cells and their molecular/macromolecular constituents;
· innovative developments in genetic and biomolecular engineering;
· computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies;
· photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design
For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.
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