2005 Fiscal Year Final Research Report Summary
CO_2 gas transporter in plasma membrane which is involved in gas exchange
| Project/Area Number |
16590053
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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, 大学院・医学薬学研究部, 助教授 (10240920)
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| Co-Investigator(Kenkyū-buntansha) |
MIYATA Takeshi Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Professor, 大学院・医学薬学研究部, 教授 (90040310)
HISATSUNE Akinori Kumamoto University, Graduate School of Pharmaceutical Sciences, Department of Chemico-Pharmacological Sciences, Assistant Professor, 大学院・医学薬学研究部, 助手 (50347001)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Gas exchange / Aquaporin / Membrane permeability / Sp1 transcription factor / Subcellular distribution |
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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. However, the mechanism of membrane gas transport has not been established. In our preliminary studies, we have found the plasma membrane CO_2 gas permeability of alveolar type I epithelial cell was unusually high, suggesting the cell has CO_2 gas transporter. Therefore, we first examined the mechanism that is involved in high CO_2 gas permeability of the cells. Primary cultured rat alveolar type II cells spontaneously differentiated into type I-like cells. We found the expression level of aquaporin-5 (AQP5) was considerably increased in this culture. Then we found that AQP5 expression in Xenopus oocytes significantly increased membrane CO_2 gas permeability. AQP5 mutants, that lack histidine or cysteine residues in its sequence, did not increased CO_2 gas permeability, suggesting the importance of these amino acids. We also examined the transcriptional regulation of AQP5 in alveolar epithelial cells, and found that Sp1 transcription factor positively and Sp3 negatively regulate AQP5 expression. In addition, we have found that retinoic acid increased AQP5 expression through the activation of Sp1. Finally, we found that nitric oxide inhibited AQP5 activity through S-nitrisylation. These findings are useful to consider the physiological regulation of gas exchange at alveolar-blood barrier.
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