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Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung
BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flu...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399815/ https://www.ncbi.nlm.nih.gov/pubmed/28431562 http://dx.doi.org/10.1186/s12931-017-0554-5 |
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author | Kuroda, Aoi Hegab, Ahmed E. Jingtao, Gao Yamashita, Shuji Hizawa, Nobuyuki Sakamoto, Tohru Yamada, Hideyasu Suzuki, Satoshi Ishii, Makoto Namkoong, Ho Asakura, Takanori Ozaki, Mari Yasuda, Hiroyuki Hamamoto, Junko Kagawa, Shizuko Soejima, Kenzo Betsuyaku, Tomoko |
author_facet | Kuroda, Aoi Hegab, Ahmed E. Jingtao, Gao Yamashita, Shuji Hizawa, Nobuyuki Sakamoto, Tohru Yamada, Hideyasu Suzuki, Satoshi Ishii, Makoto Namkoong, Ho Asakura, Takanori Ozaki, Mari Yasuda, Hiroyuki Hamamoto, Junko Kagawa, Shizuko Soejima, Kenzo Betsuyaku, Tomoko |
author_sort | Kuroda, Aoi |
collection | PubMed |
description | BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. METHODS: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 (−/−) mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 (−/−) mice. RESULTS: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 (−/−) and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 (−/−) mice. Aldh2 (−/−) tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 (−/−) mice than in WT mice. CONCLUSIONS: ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect. |
format | Online Article Text |
id | pubmed-5399815 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53998152017-04-24 Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung Kuroda, Aoi Hegab, Ahmed E. Jingtao, Gao Yamashita, Shuji Hizawa, Nobuyuki Sakamoto, Tohru Yamada, Hideyasu Suzuki, Satoshi Ishii, Makoto Namkoong, Ho Asakura, Takanori Ozaki, Mari Yasuda, Hiroyuki Hamamoto, Junko Kagawa, Shizuko Soejima, Kenzo Betsuyaku, Tomoko Respir Res Research BACKGROUND: Aldehyde dehydrogenases (ALDHs) play a major role in detoxification of aldehydes. High expression of ALDHs is a marker for stem cells of many organs including the lungs. A common polymorphism in ALDH2 gene (ALDH2*2) results in inactivation of the enzyme and is associated with alcohol flushing syndrome and increased risk for cardiovascular and Alzheimer’s diseases and some cancers. The effect of this ALDH2 polymorphism on the lung and its stem cells has not been thoroughly examined. METHODS: We examined the association between the ALDH2*2 allele and lung function parameters in a population of healthy individuals. We also examined its association with the incidence of asthma and COPD in patient cohorts. We used the in vitro colony forming assay to detect the effect of the polymorphism on lung epithelial stem cells from both primary human surgical samples and Aldh2*2 transgenic (Tg) and Aldh2 (−/−) mice. Response to acute and chronic lung injuries was compared between wild type (WT), Aldh2*2 Tg and Aldh2 (−/−) mice. RESULTS: In humans, the ALDH2*2 allele was associated with lower FEV1/FVC in the general population, but not with the development of asthma or COPD. Both the bronchial and lung epithelium carrying the ALDH2*2 allele showed a tendency for lower colony forming efficiency (CFE) compared to ALDH2 allele. In mice, the tracheal epithelial thickness, nuclear density, and number of basal stem cells were significantly lower in Aldh2 (−/−) and Aldh2*2 Tg adult mice than in WT. Electron microscopy showed significantly increased number of morphologically abnormal mitochondria in the trachea of Aldh2 (−/−) mice. Aldh2 (−/−) tracheal and lung cells showed higher ROS levels and fewer functional mitochondria than those from WT mice. No significant differences were detected when tracheal and lung epithelial stem cells were examined for their in vitro CFE. When exposed to chronic cigarette smoke, Aldh2*2 Tg mice were resistant to emphysema development, whereas influenza infection caused more epithelial damage in Aldh2 (−/−) mice than in WT mice. CONCLUSIONS: ALDH2 polymorphism has several subtle effects on the lungs, some of which are similar to changes observed during normal aging, suggesting a “premature lung aging” effect. BioMed Central 2017-04-21 2017 /pmc/articles/PMC5399815/ /pubmed/28431562 http://dx.doi.org/10.1186/s12931-017-0554-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Kuroda, Aoi Hegab, Ahmed E. Jingtao, Gao Yamashita, Shuji Hizawa, Nobuyuki Sakamoto, Tohru Yamada, Hideyasu Suzuki, Satoshi Ishii, Makoto Namkoong, Ho Asakura, Takanori Ozaki, Mari Yasuda, Hiroyuki Hamamoto, Junko Kagawa, Shizuko Soejima, Kenzo Betsuyaku, Tomoko Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title | Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title_full | Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title_fullStr | Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title_full_unstemmed | Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title_short | Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung |
title_sort | effects of the common polymorphism in the human aldehyde dehydrogenase 2 (aldh2) gene on the lung |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399815/ https://www.ncbi.nlm.nih.gov/pubmed/28431562 http://dx.doi.org/10.1186/s12931-017-0554-5 |
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