2007 Fiscal Year Final Research Report Summary
Significance of increase in aquaporin 5 expression in respiratory system
| Project/Area Number |
18590061
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Kumamoto University |
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Principal Investigator |
ISOHAMA Yoichiro Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Associate Professor (10240920)
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| Co-Investigator(Kenkyū-buntansha) |
HISATSUNE Akinori Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Associate Professor (50347001)
MIYATA Takeshi Sojo University, Faculty of Pharmaceutical Sciences, Laboratory of Presymptomatic Medical Pharmacology, Professor (90040310)
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| Project Period (FY) |
2006 – 2007
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| Keywords | alveolar epithelial cell / gas exchange / aquaporin / nitric oxide / DNA methylation |
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| Research Abstract |
O_2 and CO_2 gas transport through plasma membrane is important to maintain normal respiration between alveolar space and blood flow. We have previously indicated that aquaporins (AQPs) enhances movement of CO_2 gas, as well as water, across plasma membrane, and suggested that the increase in AQP expression might enhance gas exchange at alveoli. In this study, therefore, we first examined the mechanism of AQP5 expression in alveolar epithelial cells. It has been defined that promoter region of AQP5 gene was methylated in the cell types without AQP5, whereas it was demethylated in alveolar type I cells. The methylation of AQP5 DNA significantly decreased its transcriptional activity and the binding to Sp1 transcription factor. We have also found all-trans retinoic acid as a new AQP5 inducer. Retinoic acid increased AQP5 transcription through the activation of Sp1. In addition, we examined the effect of nitric oxide (NO), which is an important inflammatory mediator, on AQP5 activity. NO decreased AQP5 activity by S-nitrosylation of cystein residue in the water pore of AQP5.We finally, prepared CHO cells which stably express AQP5. The growth and morphology were same with those of control CHO cells without AQP5. However, the apoptosis induced by hypoxia was significantly less than that in control cells. Interestingly, glucose deprivation induced apoptosis equally in both cells, suggesting increased gas metabolism by AQP5 might inhibit hypoxia-induced apoptosis in AQP5-expressing cells. These findings are useful to consider the new strategies to enhance gas exchange at alveolar-blood barrier in various respiratory diseases.
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Research Products
(65 results)
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[Journal Article] Involvement of DNA-methylation in AQP5 gene expression in alveolar epithelial cells.(in Japanese)2008
Author(s)
Isohama, Y., Nomura, J., Harada, S., Hisatsune, A., Katsuki, H., Miyata, T.
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Journal Title
Respr Mol Med 12
Pages: 52-56
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Glycyrrhizin inhibits interleukin-8 production and NF-κB activity in lung epithelial cells, but not through glucocorticoid receptors2008
Author(s)
Takei, H., Baba, Y., Hisatsune, A., Katsuki, H., Miyata, T., Yokomizo, K., Isohama, Y.
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Journal Title
J Phamrmacol Sci 293
Pages: 460-468
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Nitric oxide decreases cell surface expression of aquaporin-5 and membrane water permeability in lung epithelial cells2007
Author(s)
Nagai, K., Watanabe, M., Seto, M., Hisatsune, A., Miyata, T., Isohama, Y.
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Journal Title
Biochem Biophys Res Commun 354
Pages: 579-584
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] TNF-alpha induces MUC1 gene transcription in lung epithelial cells : its signaling pathway and biological implication2007
Author(s)
Koga, T., Kuwahara, I., Lillehoj, EP., Lu, W., Miyata, T., Isohama, Y., Kim, KC.
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Journal Title
Am J Physiol Lung Cell Mol Physiol 293
Pages: 693-701
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The signaling pathway involved in neutrophil elastase stimulated MUC1 transcription2007
Author(s)
Kuwahara, I., Lillehoj, EP., Koga, T., Isohama, Y., Miyata, T., Kim, KC.
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Journal Title
Am J Respir Cell Mol Biol 37
Pages: 691-698
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Neutrophil elastase induces IL-8 gene transcription and protein release through p38/NF-kappaB activation via EGFR transactivation in a lung epithelial cell line2006
Author(s)
Kuwahara, I., Lillehoj, EP., Lu, W., Singh, IS., Isohama, Y., Miyata, T., Kim, KC.
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Journal Title
Am J Physiol Lung Cell Mol Physiol 291
Pages: 407-416
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] All-trans retinoic acid increases expression of aquaporin-5 and plasma membrane water permeability via transactivation of Sp1 in mouse lung epithelial cells2006
Author(s)
Nomura, J., Horie, I., Seto, M., Nagai, K., Hisatsune, A., Miyata, T., Isohama, Y.
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Journal Title
Biochem Biophys Res Commun 351
Pages: 1048-1053
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Effect of Hochu-ekki-to,a Kampo medicine, on airway inflammation2007
Author(s)
Takei, H., Koguro, N., Hisatsune, A., Miyata, T., Katsuki, H., Isohama, Y.
Organizer
The 24th annual meeting of medical and pharmaceutical society for Wakan-yaku
Place of Presentation
Tovama.
Year and Date
2007-09-08
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Transcriptional regulation of aquaporin-5 gene in alveolar epithelial cells2007
Author(s)
Isohama, Y., Nomura, J., Mikami, Y., Hirie, I., Kurauchi, Y., Hisatsune, A.
Organizer
The 5th International Conference of Aquaporin
Place of Presentation
Nara.
Year and Date
2007-07-13
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Involvement of CpG methylation in cell type-specific expression of aquaporin-5 in alveolar type I epithelial cells2007
Author(s)
Isohama, Y., Nomura, J., Harada, S., Takei, H., Hisatsune, A., Miyata, T.
Organizer
The 6th annual meeting of new aspects in pulmonary surfactant biology and diseases
Place of Presentation
Sapporo
Year and Date
2007-07-07
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Inhibition of aquaporin-5 water channel by nitric oxide2007
Author(s)
Isohama, Y., Nagai, K., Arimatsu, A., Watanabe, M., Seto, M., Hisatsune, A., Miyata, T.
Organizer
The 27th annual meeting of the Japanese association for airway secretion research
Place of Presentation
Kagoshima
Year and Date
2007-04-14
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Nitric oxide stimulates aquaporin-5 endocytosis through cGMP-independent pathway in lung epithelial cells2007
Author(s)
Watanabe, M., Nagai, K., Arimatsu, A., Hisatsune, A., Miyata, T., Isohama, Y.
Organizer
The 80th annual meeting of the Japanese pharmacological society
Place of Presentation
Nagoya
Year and Date
2007-03-16
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Transcriptional regulation of MUC1 gene by neutrophil elastase,through Sp1 binding to the MUC1 promoter2006
Author(s)
Hisatsune, A., Kalahari, I., Isohama, Y., Kim, KC., Miyata, T.
Organizer
The 26th annual meeting of the Japanese association for airway secretion research
Place of Presentation
Tokyo
Year and Date
2006-04-22
Description
「研究成果報告書概要(欧文)」より
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