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Respiratory Research
Published in: Respiratory Research 1/2020

01-12-2020 | Chronic Obstructive Lung Disease | Research

Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model

Authors: Huihui Zeng, Tiao Li, Xue He, Shan Cai, Hong Luo, Ping Chen, Yan Chen

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Emphysema is a crucial pathological characteristic of chronic obstructive pulmonary disease (COPD). Oxidative stress, apoptosis and epigenetic mechanisms contribute to the pathogenesis of emphysema. However, an attempt to accurately identify whether these mechanisms interact with each other and how they are triggered has never been conducted.

Method

The total reactive oxygen species (ROS) level, pulmonary apoptosis and B-cell lymphoma/leukemia-2 (Bcl-2) expression, an apoptosis regulator, were detected in samples from COPD patients. Bisulfite sequencing PCR (BSP) was conducted to observe the alterations in the methylation of the Bcl-2 promoter in specimens. The dysregulation of DNA methyltransferase enzyme 1 (DNMT1), a vital DNA methyltransferase enzyme, in the lungs of patients was confirmed through western blotting. To find out interactions between oxidative stress and DNA methylation in emphysema, mouse models were built with antioxidant treatment and DNMT1 silencing, and were examined with the pulmonary apoptosis, Bcl-2 and DNMT1 levels, and epigenetic alterations of Bcl-2.

Results

Higher ROS levels and pulmonary apoptosis were observed in COPD patients than in healthy controls. Downregulated Bcl-2 expression with increased promoter methylation and DNMT1 protein expression was found in COPD patients. Antioxidant treatment reduced the level of ROS, DNMT1 protein and emphysematous progression in the smoking models. Following DNMT1 blockade, smoking models showed improved lung function, pulmonary apoptosis, emphysematous progression, and increased Bcl-2 protein level with less promoter methylation than emphysema mice.

Conclusion

Cigarette-induced oxidative stress mediates pulmonary apoptosis and hypermethylation of the Bcl-2 promoter in emphysema models through DNMT1.
Appendix
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Metadata
Title
Oxidative stress mediates the apoptosis and epigenetic modification of the Bcl-2 promoter via DNMT1 in a cigarette smoke-induced emphysema model
Authors
Huihui Zeng
Tiao Li
Xue He
Shan Cai
Hong Luo
Ping Chen
Yan Chen
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01495-w

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