| Project/Area Number |
06454294
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kansai Medical University |
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Principal Investigator |
INADA Mitsuo Kansai Medical University, Department of Medicine, Professor, 医学部, 教授 (90115791)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUBARA Hiroaki Kansai Medical University, Department of Medicine, Associate Professor, 医学部, 講師 (10239072)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 1995: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1994: ¥4,600,000 (Direct Cost: ¥4,600,000)
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| Keywords | Angiotensin II / Receptor / Gene / Transcription / myocyte / neuron / アルギオテンシンII / 糖質ステロイドホルモン |
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| Research Abstract |
Angiotensin II mediates vasoconstrictive and cell proliferative action through its specific receptor (AT1-R) in cardiovascular system. AT1-R expression is regulated in a cell-specific manner : the expression is abundant in vascular smooth muscle cells but very low in neurons. We examined the transcriptional mechanism of AT1-R gene and its expression profile in cardiac remodeling.
AT1-R gene consisted of three exons and third exon contains the whole open reading frame. There are three positive cis-regulatory elements and one strong negative cis-regulatory element (NRE, -489 - -331) in 5' flanking region. NRE is active only in PC12 cells but not in other cell types, such as vascular smooth muscle cells or skeletal muscle cells. Southwestern blot analyses revealed that 53KDa nuclear protein is bound to the NRE that exists in PC12 cell and brain, but not in other tissues, suggesting that this protein determines the expression pattern of AT1-R in neurons.
Expression levels of AT1-R are upregulated in hypertrophied ventricles and myocardial infarction. This regulation was mediated through gene transcription. Thus, expression of AT1-R is increased in cardiac remodeling, which suggests the effect of angiotensin II is enhanced in such pathological conditions.
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