Cigarette smoke induces the ROS accumulation and iNOS activation through deactivation of Nrf-2/SIRT3 axis to mediate the human bronchial epithelium ferroptosis

作者全名："Zi, Yawan; Wang, Xiaohui; Zi, Yafei; Yu, Huilin; Lan, Yuan; Fan, Yuchen; Ren, Cheng; Liao, Ke; Chen, Hong"

作者地址："[Zi, Yawan; Wang, Xiaohui; Yu, Huilin; Lan, Yuan; Fan, Yuchen; Ren, Cheng; Liao, Ke; Chen, Hong] Chongqing Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Chongqing 400016, Peoples R China; [Zi, Yawan; Zi, Yafei] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Ophthalmol, Chongqing 400016, Peoples R China"

通信作者："Liao, K; Chen, H (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Pulm & Crit Care Med, Chongqing 400016, Peoples R China."

来源：FREE RADICAL BIOLOGY AND MEDICINE

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000952625900001

JCR分区：Q1

影响因子：7.4

年份：2023

卷号：200

期号：　

开始页：73

结束页：86

文献类型：Article

关键词：Ferroptosis; Cigarette smoke; ROS; iNOS; Nrf-2/SIRT3

摘要："Cigarette smoke (CS)-induced oxidative stress drives the pathogenesis of respiratory diseases, in which the activation and accumulation of reactive oxygen species (ROS) play an important role. Ferroptosis, a regulated cell death induced by Fe2+-dependent, lipid peroxidation, and ROS, is closely related to CS-induced airway injury disease, but its mechanism remains unclear. We found that bronchial epithelial ferroptosis and expression of iNOS in smoking patients were significantly higher than that in non-smokers. The iNOS, induced by CS exposure, was involved in bronchial epithelial cell ferroptosis, whereas genetic depletion or pharmacologic inactivation of iNOS attenuated the CS-induced ferroptosis and mitochondrial dysfunction. Our mechanistic studies found that SIRT3 directly bound to and negatively regulated iNOS to mediate ferroptosis. Moreover, we found that the Nrf-2/SIRT3 signal was deactivated by cigarette smoke extract (CSE)-induced ROS. Collectively, these results linked CS to human bronchial epithelial cell ferroptosis through ROS deactivation of the Nrf-2/SIRT3 signal to promote iNOS expression. Our study provides new insights into the pathogenesis of CS-induced tracheal injury diseases such as chronic bronchitis, emphysema, and chronic obstructive pulmonary disease."

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