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Regulation of differentiation and reproduction of vascular organs by Edg receptor expression

Edg受体表达对血管器官分化和繁殖的调节

基本信息

批准号：
15590064
负责人：
MURAKI Katsuhiko
金额：
$ 2.24万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

Objective: Palmitoyl-L-carnitine (palcar), which accumulates in ischemic heart, affects cellular functions of vascular endothelium in the ischemic area. The aim of the study was to examine the effects of palcar on intracellular Cat^<2+> concentration ([Ca^<2+>]i) in vascular endothelial cells in comparison with those of sphingosine-1-phosphate (S1P) and to investigate the underlying mechanisms. Methods and Results: Human umbilical vein endothelial cells (huvecs) were loaded with Fura-2 AM and the fluorescence signal was measured with Argus 50/CA imaging system. Application of palcar at a concentration range between 0.3 and 3μM elevated [Ca^<2+>]i i in huvecs and its potency was about 30 times lower than that of S1P. Although the sensitivity to palcar and S1P varied widely among huvecs from individuals, response to 3 μM palcar in each huvec clearly paralleled that to 0.3 μM S1P (r=0.79, P<0.001). In addition, huvecs that were treated with 100 ng/ml pertussis toxin (PTX) for 15 hr failed to respond to palcar as well as to S1P, but did respond to 3 μM His. On the other hand, pre-treatment of huvecs with palcar abolished subsequent S1P-induced elevation of [Ca^<2+>]i, but not the His-induced elevation. Conclusions: Our data indicate that palcar has a novel action on huvecs as a potential agonist of receptors for S1P. Effective inhibition of response to S1P by palcar suggests that palcar affects angiogenesis regulated by S1P.

目的：棕榈酰-L-卡尼汀（palmitoyl-L-carnitine，palcar）在缺血心脏中蓄积，影响缺血区血管内皮细胞功能。本研究的目的是检测palcar对血管内皮细胞内Cat^<2+>浓度（[Ca^<2+]i）的影响，并与1-磷酸鞘氨醇（S1 P）进行比较，探讨其潜在的机制。方法和结果：用Fura-2 AM负载人脐静脉内皮细胞（Human umbilical vein endothelial cells，huvecs），Argus 50/CA成像系统检测荧光信号。在0.3 ~ 3μM浓度范围内应用palcar可使HUVECs内[Ca^<2+>] i升高，其效力比S1 P低约30倍。虽然不同个体的huvec对palcar和S1 P的敏感性差异很大，但每个huvec对3 μM palcar的反应明显高于对0.3 μM S1 P的反应（r=0.79，P<0.001）。此外，用100 ng/ml百日咳毒素（PTX）处理15小时的huvec对palcar和S1 P没有反应，但对3 μM His有反应。另一方面，用palcar预处理huvecs可以消除随后S1 P诱导的[Ca^<2+>]i升高，但不能消除His诱导的升高。结论：我们的数据表明，palcar作为一种潜在的S1 P受体激动剂，对人脐静脉内皮细胞有一种新的作用。palcar对S1 P反应的有效抑制表明palcar影响由S1 P调节的血管生成。