Affiliation:
1. Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
2. 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
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.
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.
method:
In the present study, the mouse model of COPD was established by cigarette smoking (CS), and mouse alveolar epithelial (MLE-12) cells were treated with cigarette smoke extract (CSE). TUNEL assay, RT-PCR and western blot were performed to evaluate effects of NAC on apoptosis, endoplasmic reticulum (ER) stress and mitochondrial dysfunction. Meanwhile, L-Buthionine-sulfoximine (BSO), a GSH inhibitor, was used to uncover the mechanism of COPD treatment by NAC.
Results::
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.
other:
No
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmaceutical Science,Biotechnology