N-acetylcysteine Attenuates Cigarette Smoke-induced Alveolar Epithelial Cell Apoptosis through Reactive Oxygen Species Depletion and Glutathione Replenish In vivo and In vitro

Title:N-acetylcysteine Attenuates Cigarette Smoke-induced Alveolar Epithelial Cell Apoptosis through Reactive Oxygen Species Depletion and Glutathione Replenish In vivo and In vitro

Volume: 25 Issue: 11

Author(s): Jie Zhao, Mi Han, Yange Tian, Peng Zhao, Xuefang Liu, Haoran Dong, Suxiang Feng and Jiansheng Li*

Affiliation:

• Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases co-constructed by Henan Province & Education Ministry of P.R. China, Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, 450000, China
• The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China

Keywords: N-acetylcysteine, COPD, alveolar epithelial cell, apoptosis, reactive oxygen species, glutathione.

Abstract: Background: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide. N-acetylcysteine (NAC) is well known for its antioxidant properties, along with potential protective effects on COPD. However, the molecular mechanism of NAC against the apoptosis of alveolar epithelial cells (AECs) in COPD remains unclear.

Objective: This study aimed to explore the anti-apoptosis effect of NAC in COPD mice and alveolar epithelial cells.

Methods: In the present study, the mouse model of COPD was established by cigarette smoke (CS), and mouse alveolar epithelial (MLE-12) cells were treated with cigarette smoke extract (CSE). TdT-mediated dUTP nick-end labeling (TUNEL) assay, reverse transcription polymerase chain reaction (RT-PCR), and western blot were performed to evaluate the effects of NAC on apoptosis, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction. Meanwhile, LButhionine- sulfoximine (BSO), a glutathione (GSH) inhibitor, was used to uncover the mechanism of COPD treatment by NAC.

Results: We found that NAC pretreatment could attenuate the protein levels of apoptosis, ER stress, and mitochondrial dysfunction-related genes caused by CS in vivo. Meanwhile, CSE could decrease MLE-12 cell viability, which was prevented by apoptosis inhibitor ZVAD-FMK but not necroptosis inhibitor necrostatin-1. Pretreatment of MLE-12 cells with NAC increased cellular GSH levels, inhibited cellular and mitochondrial reactive oxygen species (ROS) accumulation, and decreased protein level of apoptosis, ER stress, and mitochondrial dysfunctionrelated genes. Moreover, experiment results showed that BSO could completely reverse the beneficial effects of NAC.

Conclusion: Our study confirmed that NAC can attenuate CS-induced AEC apoptosis via alleviating ROS-mediated ER stress and mitochondrial dysfunction pathway, and the mechanism was found to be related to replenishing the cellular GSH content.

Cite this article as:

Zhao Jie, Han Mi, Tian Yange, Zhao Peng, Liu Xuefang, Dong Haoran, Feng Suxiang and Li Jiansheng*, N-acetylcysteine Attenuates Cigarette Smoke-induced Alveolar Epithelial Cell Apoptosis through Reactive Oxygen Species Depletion and Glutathione Replenish In vivo and In vitro, Current Pharmaceutical Biotechnology 2024; 25 (11) . https://dx.doi.org/10.2174/0113892010257526231019143524