Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
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
_version_ 1783230711074914304
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
work_keys_str_mv AT kurodaaoi effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT hegabahmede effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT jingtaogao effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT yamashitashuji effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT hizawanobuyuki effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT sakamototohru effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT yamadahideyasu effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT suzukisatoshi effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT ishiimakoto effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT namkoongho effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT asakuratakanori effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT ozakimari effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT yasudahiroyuki effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT hamamotojunko effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT kagawashizuko effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT soejimakenzo effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung
AT betsuyakutomoko effectsofthecommonpolymorphisminthehumanaldehydedehydrogenase2aldh2geneonthelung