EFFCTS OF ANOVEL NTERACTING MOLECULE OFAT1 RECEPTOR ON RENAL FUNCTION
Project/Area Number |
18590897
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Yokohama City University |
Principal Investigator |
TAMURA Kouichi Yokohama City University, GARDUATE SCHOOL OF MEDICINE, DEPARTMENT OF CARDIORENAL MEDICINE, ASSOCIATE PROFESSOR (40285143)
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Co-Investigator(Kenkyū-buntansha) |
HORIUCHI Masatsugu EHIME UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL BIOCHEMISTRY, CHAIRMAN & PROFESSOR (40150338)
UMEMURA Satoshi YOKOHAMA CITY UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF MEDICAL SCIENCE AND CARDIORENAL MEDICINE, CHAIRMAN & PROFESSOR (00128589)
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Project Period (FY) |
2006 – 2007
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Project Status |
Completed (Fiscal Year 2007)
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Budget Amount *help |
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2007: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
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Keywords | Signaling / Blood pressure regulation / Interacting molecule / Bioactivity / Translational research |
Research Abstract |
Chronic elevations of circulating angiotensin II (Ang II) cause sustained hypertension and enhanced accumulation of intrarenal Ang II by an Ang II type 1 receptor (AT1 receptor) -dependent process. Previous studies showed that the C-terminal cytoplasmic domain of AT1 receptor is involved in the control of receptor internalization and in linking receptor-mediated signal transduction to the specific biological response. We previously cloned a novel molecule ATRAP (AT1 receptor-associated protein) that specifically interacts with C-terminal of AT1 receptor. The results of previous in vitro studies showed that ATRAP specifically inhibits AT1 receptor signaling by constitutive activation of AT1 receptor internalization to decrease cell surface AT1 receptor number. The present study tested the hypothesis that chronic elevations in circulating Ang II regulate ATRAP protein expression in a tissue-specific manner. C57BL6 mice were infused with Ang II (1,000 ng/kg/min)or vehicle subcutaneously f
… More
or 14 days via osmotic minipump. On day 12, systolic blood pressure averaged 176+/-1.0 mm Hg in Ang II-infused mice compared with mice given vehicle (122+/-4 mm Hg) .Western blot analysis using the anti-AT1 receptor and anti-ATRAP antibodies was performed. The results showed that AT1 receptor protein levels in the kidney and liver were comparable in Ang II- and vehicle-infused mice. In contrast, ATRAP protein levels were significantly decreased in the kidney of Ang II-infused mice (51% decrease; P<0.05). ATRAP protein levels in the liver were also similar in the two groups. Therefore, these "results indicate that renal and liver AT1 receptor gene expression is maintained but renal ATRAP gene expression is specifically suppressed in Ang II-induced hypertension. The renal-specific down-regulation of the ratios of ATRAP/AT1 receptor expression by Ang II infusion causes the relative predominance of AT1 receptor signaling over inhibition by ATRAP in the kidney and thus allows the sustained effects of chronic elevations in Ang II to elicit progressive increases in blood pressure. Less
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Report
(3 results)
Research Products
(20 results)
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[Journal Article] regulatory effect of angiotensin II type 1 receptor-interacting molecule on vascular smooth muscle cells2007
Author(s)
Azuma, K., Tamura, K., Shigenaga, A., Wakui, H., Masuda, S.,Tsurumi-lkeya, Y., Tanaka, Y., Sakai, M., Matsuda, M., Hashimoto, T., Ishigami, T., Lopez-llasaca, M., Umemura, S
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Journal Title
Hypertension 50
Pages: 926-932
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Expression of MAK-V/Hunk in renal distal tubules and its possible involvement in proliferative suppression2007
Author(s)
Sakai, M., Tamura, K., Tsurumi, Y., Tanaka, Y., Koide, Y., Matsuda, M., Ishigami, T., Yabana, M., Tokita, Y., Hiroi, Y., Komuro, I., Umemura, S
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Journal Title
Am J Physiol Renal Physiol 292
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] The role of angiotensin AT1 receptor-associated protein in renirr-angiotensin system regulation and function2007
Author(s)
Tamura, K., Tanaka, Y., Tsurumi, Y., Azuma, K., Shigenaga, A., Wakui, H., Masuda, S., Matsuda, M
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Journal Title
Curr Hypertens Rep 9
Pages: 121-127
Description
「研究成果報告書概要(欧文)」より
Related Report
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