Clinical and molecular biological approach to the genesis of coronary artery spasm : A study on the role of p122 protein

冠状动脉痉挛发生的临床和分子生物学方法：p122 蛋白作用的研究

• 批准号: 20590856
• 负责人: OKUMURA Ken
• 金额: $ 3万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590856/
• 关键词: 循環器・高血圧; 冠攣縮; P122蛋白; Phospholipase C; phospholipase C; Dhospholipase C

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

p122蛋白最近被克隆以增强磷脂酶C（PLC）-δ1活性。为了研究p122在增强血管运动性中的作用，我们检测了培养的皮肤成纤维细胞中p122的表达，细胞内钙浓度（[Ca^<2+] i），细胞内钙浓度（[Ca^<2+] i）在基线和乙酰胆碱刺激后，转染p122的细胞，以及基因组DNA中的启动子。p122蛋白和基因表达水平在冠状动脉痉挛组（n=11）明显高于对照组（n=9）（均P<0.01）。[Ca p122转染的细胞中，基线时的[Ca^<2 +>] i和乙酰胆碱引起的[Ca^<2+>] i峰值增加都是未转染p122的细胞的两倍。在p122启动子分析中，-228G/A和-1466C/T变异体显示荧光素酶活性增加。-228G/A变异在男性患者中比在男性对照中更常见（p<0.05）。总之，p122在冠状动脉痉挛患者中上调，这导致乙酰胆碱[Ca^<2+>]_i增加，从而似乎与冠状动脉血管运动增强有关

项目成果

Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells.

• DOI: 10.1093/cvr/cvn356
• 发表时间: 2008-12
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: T. Osanai;H. Tomita;M. Kushibiki;M. Yamada;Makoto Tanaka;Toshihiro Ashitate;Takashi Echizen;C. Katoh;K. Magota;K. Okumura

Coronary Vasospasm Induced In Transgenic Mice With Variant Phospholipase C-δ1(R257H)

磷脂酶 C-δ1 变体（R257H）转基因小鼠诱导冠状动脉痉挛

• 发表时间: 2010
• 作者: Shibutani S;Ken Okumura;et al
• 通讯作者: et al

Management of Atrial Fibrillation : Medical or Ablation

心房颤动的治疗：药物或消融

• 发表时间: 2009
• 作者: 宮本正章;高木元;高木郁代;加藤浩司;太良修平;桐木園子;高野仁司;安武正弘;水野杏一;水野博司;田畑泰彦;松範子;黄川田信允;大石沙織;内田英二;徳永昭;奥村謙
• 通讯作者: 奥村謙

Brain natriuretic peptide is released from human astrocytoma cell line U373MG under hypoxia: a possible role in anti-apoptosis

• DOI: 10.1677/joe-10-0230
• 发表时间: 2011-01-01
• 期刊: JOURNAL OF ENDOCRINOLOGY
• 影响因子: 4
• 作者: Katoh, Chisato;Osanai, Tomohiro;Okumura, Ken
• 通讯作者: Okumura, Ken

Effect of pilsicainide on dominant frequency in the right and left atria and pulmonary veins during atrial fibrillation : Association with its atrial fibrillation terminating effect

匹西卡尼对心房颤动期间左右心房和肺静脉主频率的影响：与其心房颤动终止作用的关联

• 发表时间: 2009
• 期刊: Eur J Pharmacol 608
• 作者: Horiuchi D;Iwasa A;et al
• 通讯作者: et al