Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung
Abstract 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 alc...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2017-04-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12931-017-0554-5 |
| _version_ | 1818416568272420864 |
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| author | Aoi Kuroda Ahmed E. Hegab Gao Jingtao Shuji Yamashita Nobuyuki Hizawa Tohru Sakamoto Hideyasu Yamada Satoshi Suzuki Makoto Ishii Ho Namkoong Takanori Asakura Mari Ozaki Hiroyuki Yasuda Junko Hamamoto Shizuko Kagawa Kenzo Soejima Tomoko Betsuyaku |
| author_facet | Aoi Kuroda Ahmed E. Hegab Gao Jingtao Shuji Yamashita Nobuyuki Hizawa Tohru Sakamoto Hideyasu Yamada Satoshi Suzuki Makoto Ishii Ho Namkoong Takanori Asakura Mari Ozaki Hiroyuki Yasuda Junko Hamamoto Shizuko Kagawa Kenzo Soejima Tomoko Betsuyaku |
| author_sort | Aoi Kuroda |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-14T11:52:57Z |
| format | Article |
| id | doaj.art-99dab1cd5f8040c1aa344f4e038ef6c9 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-12-14T11:52:57Z |
| publishDate | 2017-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-99dab1cd5f8040c1aa344f4e038ef6c92022-12-21T23:02:14ZengBMCRespiratory Research1465-993X2017-04-0118111810.1186/s12931-017-0554-5Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lungAoi Kuroda0Ahmed E. Hegab1Gao Jingtao2Shuji Yamashita3Nobuyuki Hizawa4Tohru Sakamoto5Hideyasu Yamada6Satoshi Suzuki7Makoto Ishii8Ho Namkoong9Takanori Asakura10Mari Ozaki11Hiroyuki Yasuda12Junko Hamamoto13Shizuko Kagawa14Kenzo Soejima15Tomoko Betsuyaku16Division of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineBeijing Chest Hospital, Beijing Tuberculosis and Thoracic Tumor Research Institute, Capital Medical UniversityDepartment of Pathology, Keio University School of MedicineDepartment of Pulmonary Medicine, Faculty of Medicine, University of TsukubaDepartment of Pulmonary Medicine, Faculty of Medicine, University of TsukubaDepartment of Pulmonary Medicine, Faculty of Medicine, University of TsukubaDepartment of Thoracic Surgery, Japanese Red Cross Ishinomaki HospitalDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineDivision of Pulmonary Medicine, Department of Medicine, Keio University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12931-017-0554-5ALDH2AldehydeEpithelial cellBasal cellClub cellTrachea |
| spellingShingle | Aoi Kuroda Ahmed E. Hegab Gao Jingtao Shuji Yamashita Nobuyuki Hizawa Tohru Sakamoto Hideyasu Yamada Satoshi Suzuki Makoto Ishii Ho Namkoong Takanori Asakura Mari Ozaki Hiroyuki Yasuda Junko Hamamoto Shizuko Kagawa Kenzo Soejima Tomoko Betsuyaku Effects of the common polymorphism in the human aldehyde dehydrogenase 2 (ALDH2) gene on the lung Respiratory Research ALDH2 Aldehyde Epithelial cell Basal cell Club cell Trachea |
| 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 | ALDH2 Aldehyde Epithelial cell Basal cell Club cell Trachea |
| url | http://link.springer.com/article/10.1186/s12931-017-0554-5 |
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