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Protective effect of demethylation treatment on cigarette smoke extract-induced mouse emphysema model.
- Source :
-
Journal of pharmacological sciences [J Pharmacol Sci] 2013; Vol. 123 (2), pp. 159-66. - Publication Year :
- 2013
-
Abstract
- In the present study, we explored the effects of demethylation in a cigarette smoke extract (CSE)-induced mouse emphysema model. Animals were randomly assigned to the control group, CSE group, 5-aza-2'-deoxycytidine (AZA) group, and CSE+AZA group (n = 10 per group). The mitochondrial transcription factor A (mtTFA) promoter methylation increased over 4-fold in the CSE group compared with the control group, which was reversed by AZA. The mtTFA and the cytochrome c oxidase subunit II (COX II) mRNA and protein levels were decreased approximately 3-fold in the CSE group compared with the control group, which was largely restored by AZA. Histological analysis showed that the CSE group exhibited emphysema compared with the control, which was alleviated by AZA. In addition, CSE significantly induced lung cell apoptosis and decreased lung function and lung mitochondrial COX activity, which was mostly restored by AZA. In conclusion, we for the first time provide evidence that demethylation therapy with AZA can effectively improve emphysema, lung function, lung cell apoptosis, and lung mitochondrial COX activity in a CSE-induced mouse emphysema model, which adds fresh insight into the therapeutic potential of demethylating agents in the prevention and treatment of cigarette smoke-induced emphysema.
- Subjects :
- Animals
Apoptosis drug effects
Azacitidine pharmacology
Azacitidine therapeutic use
DNA-Binding Proteins metabolism
Decitabine
Electron Transport Complex IV genetics
Electron Transport Complex IV metabolism
Emphysema drug therapy
Emphysema pathology
Lung cytology
Male
Mice
Mice, Inbred BALB C
Mitochondria enzymology
Mitochondrial Proteins metabolism
RNA, Messenger metabolism
Transcription Factors metabolism
Azacitidine analogs & derivatives
Disease Models, Animal
Emphysema etiology
Emphysema prevention & control
Methylation drug effects
Smoking adverse effects
Subjects
Details
- Language :
- English
- ISSN :
- 1347-8648
- Volume :
- 123
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 24141367
- Full Text :
- https://doi.org/10.1254/jphs.13072fp