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Studies on molecular cell biology of the inhibition of coronary vasoconstriction and intimal thickening.

抑制冠状血管收缩和内膜增厚的分子细胞生物学研究。

基本信息

批准号：
07407022
负责人：
KANAIDE Hideo
金额：
$ 14.66万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1998
项目状态：
已结题

项目摘要

For the prevention of coronary vasoconstriction and intimal thickening, following studies were performed : In smooth muscle and endothelial cells, (1)the characterization of the intracellular signal transduction networks, (2) the elucidation of the relationships between cell cycle progression and the cellular functions, and (3) the elucidation of the relationships between signaling factors and cellular functions/structures. (4) The clinical applicatopn of the results of these experimental studies.Following results/conclusions were obtained : (1) We have developed a method to monitor [Ca]i changes of the vascular strips, which was reported as the chapter "Measurement of [Ca]i in smooth muscle strips using front-suface fluorimetry" (P269-P277) by H.Kanaide in the book "Calcium signaling protocols" edited by David G.Lambert, which is the Vol.114, of series of "Methods in Molecular Biology" (Humana Press Inc., Totowa, NJ, USA, 1999). Using this technique and skinning of cell membrane, we have characterized the signal transduction system of smooth muscle and endothelial cells. In particular, we have characterized the Ca-sensitivity of the contractile apparatus in smooth muscle cells and relationships between [Ca]i and NO production in endothelial cells. (2) We found that types of Ca-channels(T,L) varied during the progression of cell cycles in smooth muscle cells. There appeared submembranous localization of myosin phosphatase at the phase of contact inhibition of the growth in endothelial cells. (3) Using DNA mutants, we have characterized the relationships between protein structure and funtion of calmodulin and 130 and 20 KDa subunits of myosin phosphatase. (4) There is a mutation of Trp64Arg in DNA of beta 3 adrenoceptors among the patients with ischemic heart disease. However, the clinical application of the results of the present study has remained to be the next problem which confronts us.

为了预防冠状动脉血管收缩和内膜增厚，进行了以下研究：在平滑肌和内皮细胞中，（1）细胞内信号转导网络的表征，（2）阐明细胞周期进程与细胞功能之间的关系，（3）阐明信号传导因子与细胞功能/结构之间的关系。(4)这些实验研究结果的临床应用。获得了以下结果/结论：（1）我们建立了一种监测血管平滑肌条[Ca]i变化的方法，该方法已被报道为“用前表面荧光法测定平滑肌条[Ca]i”一章。（P269-P277），由H.Kanaide在大卫G.Lambert编辑的书“钙信号协议”中，其是“分子生物学方法”系列的第114卷（Humana Press Inc.，Totowa，NJ，USA，1999）。利用这种技术和皮肤的细胞膜，我们的特点是平滑肌和内皮细胞的信号转导系统。特别是，我们的特点是钙敏感性的收缩装置在平滑肌细胞和[Ca]i和NO的产生在内皮细胞之间的关系。(2)我们发现，在平滑肌细胞的细胞周期的进程中，钙通道的类型（T，L）的变化。在内皮细胞生长的接触抑制期，肌球蛋白磷酸酶出现膜下定位。(3)利用DNA突变体，我们研究了钙调素与肌球蛋白磷酸酶130和20 KDa亚基的蛋白质结构和功能之间的关系。(4)缺血性心脏病患者β_3肾上腺素能受体DNA中存在Trp 64 Arg突变。然而，本研究结果的临床应用仍然是我们面临的下一个问题。