2003 Fiscal Year Final Research Report Summary
Molecular mechanisms of endothelial mechanosensitivity.
| Project/Area Number |
14570081
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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 |
General pharmacology
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| Research Institution | Kyushu University |
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Principal Investigator |
OIKE Masahiro Kyushu University, Graduate School of Medical Sciences, Lecturer, 大学院・医学研究院, 講師 (70271103)
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| Project Period (FY) |
2002 – 2003
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| Keywords | endothelium / mechanosensitivity / ATP / calcium / Dbl protein / tyrosine kinase / small G protein / actin |
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| Research Abstract |
This study aimed to clarify the molecular mechanisms of mechanosensitive responses in human umbilical vein endothelial cells (HUVECs). The results obtained in the present study are as follows ;
(1)Identification of Dbl protein involved in hypotonic stress-induced responses : It is known that the activation of Rho requires Dbl family protein. RT-PCR analysis revealed that HUVECs express mRNAs of S Dbl family proteins including Abr, Fgd-1, Kalirin-7, and Lbc. We examined the effects of the antisense oligonucleotides against these m-RNAs on hypotonic stress (HTS)-induced Ca^<2+> transients, and found that the antisense against Lbc suppressed it. Furthermore, overexpression of Lbc cDNA augments HTS-induced Ca^<2+> transients. These suggest that mechanical stress induces the activation of Rho in HUVECs via Lbc.
(2)Interrelation between HTS-induced tyrosine kinase activation and Rho activation : HTS-induced activation of two tyrosine kinases, FAK and paxillin, was detect with Western blotting. Tyrosine kinase inhibitors suppressed ATP release induced by lysophosphatidic acid (LPA), which activates Rho. Furthermore, HTS-induced tyrosine phosphorylation of FAK and paxillin was suppressed by Rho-kinase inhibitor Y27632. These indicate that HTS-induced responses are obtained by the sequential activation of FAK/paxillin followed by Rho/Rho-kinase.
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Research Products
(10 results)
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[Publications] Hisadome, K., Koyama, T., Kimura, C., Droogmand, G, Ito, Y., Oike, M: "Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells."Journal of General Physiology. 119. 511-520 (2002)
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「研究成果報告書概要(和文)」より
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[Publications] Kimura, C., Cheng, W., Hisadome, K., Wang, Y.P., Koyama, T., Karashima, Y., Oike, M., Ito, Y.: "Superoxide anion impairs contractility in cultured aortic smooth muscle cells."American Journal of Physiology. 283. H382-H390 (2002)
Description
「研究成果報告書概要(和文)」より
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[Publications] Hisadome, K., Koyama, T., Kimura,.C., Droogmans, G., Ito, Y., Gike, M.: "Volume-regulated anion channels serve as an auto/paracrine nucleotide release pathway in aortic endothelial cells."Journal of General Physiology. 119-6. 511-520 (2002)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kimura, C., Cheng, W., Hisadome, K., Wang, Y.P., Koyama, T., Karashima, Y., Oike, M., Ito, Y.: "Superoxide anion impairs contractility in cultured aortic smooth muscle cells."American Journal of Physiology. 283-1. H382-H390 (2002)
Description
「研究成果報告書概要(欧文)」より
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