Premium
Reactive oxygen and nitrogen species induce cell apoptosis via a mitochondria‐dependent pathway in hyperoxia lung injury
Author(s) -
Zou Dongmei,
Li Jing,
Fan Qianqian,
Zheng Xuemei,
Deng Jian,
Wang Shaohua
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27382
Subject(s) - hyperoxia , apoptosis , mitochondrion , reactive oxygen species , microbiology and biotechnology , reactive nitrogen species , programmed cell death , biology , lung , chemistry , biochemistry , medicine
Hyperoxia‐induced lung injury limits the application of mechanical ventilation on rescuing the lives of premature infants and seriously ill and respiratory failure patients, and its mechanisms are not completely understood. In this article, we focused on the relationship between hyperoxia‐induced lung injury and reactive oxygen species (ROS), reactive nitrogen species (RNS), mitochondria damage, as well as apoptosis in the pulmonary epithelial II cell line RLE‐6TN. After exposure to hyperoxia, the cell viability was significantly decreased, accompanied by the increase in ROS, nitric oxide (NO), inflammatory cytokines, and cell death. Furthermore, hyperoxia triggered the loss of mitochondrial membrane potential (▵Ψm), thereby promoting cytochrome c to release from mitochondria to cytoplasm. Further studies conclusively showed that the Bax/Bcl‐2 ratio was enlarged to activate the mitochondria‐dependent apoptotic pathway after hyperoxia treatment. Intriguingly, the effects of hyperoxia on the level of ROS, NO and inflammation, mitochondrial damage, as well as cell death were reversed by free radical scavengers N‐acetylcysteine and hemoglobin. In addition, a hyperoxia model of neonatal Sprague‐Dawley (SD) rats presented the obvious characteristics of lung injury, such as a decrease in alveolar numbers, alveolar mass edema, and disorganized pulmonary structure. The effects of hyperoxia on ROS, RNS, inflammatory cytokines, and apoptosis‐related proteins in lung injury tissues of neonatal SD rats were similar to that in RLE‐6TN cells. In conclusion, mitochondria are a primary target of hyperoxia‐induced free radical, whereas ROS and RNS are the key mediators of hyperoxia‐induced cell apoptosis via the mitochondria‐dependent pathway in RLE‐6TN cells.