2010 Fiscal Year Final Research Report
Clinical and molecular biological approach to the genesis of coronary artery spasm : A study on the role of p122 protein
| Project/Area Number |
20590856
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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 |
Circulatory organs internal medicine
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| Research Institution | Hirosaki University |
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Principal Investigator |
OKUMURA Ken Hirosaki University, 大学院・医学研究科, 教授 (20185549)
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| Co-Investigator(Kenkyū-buntansha) |
OSANAI Tomohiro 弘前大学, 大学院・医学研究科, 准教授 (00169278)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 循環器・高血圧 / 冠攣縮 / P122蛋白 / Phospholipase C |
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| Research Abstract |
A p122 protein was recently cloned to potentiate phospholipase C (PLC)-δ1 activity. To investigate the role of p122 in the enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular calcium concentration ([Ca^<2+>]_i) at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA. p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with that in control subjects (n=9) (both p<0.01). [Ca^<2+>]_i at baseline and the peak increase in [Ca^<2+>]_i in response to acetylcholine were both two times higher in cells transfected with p122 than in those without p122. In the p122 promoter analysis, the -228G/A and -1466C/T variants revealed the increase in luciferase activitiy. The -228G/A variant was more frequent in male patients than in male controls (p<0.05). In conclusions, p122 is upregulated in patients with coronary spasm, which causes increased [Ca^<2+>]_i to acetylcholine and thereby seems to be related to enhanced coronary vasomotility
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