血管生成素-1激活tyrosine kinase／PI3K增加血管内皮细胞[Mg^2＋]i  

Angiopoietin-1 increases intracellular free Mg^(2+) by tyrosine kinase/PI3K in HUVECs

作　　者：谢同杰[1] 洪炳哲[1] 李胜范[2] 王丽萍[1] 朴海南[1] 高立建[3] 刘学田[1] 陈毓婷 

机构地区：[1]大连大学附属新华医院心内科,辽宁大连116021 [2]中国医学科学院中国协和医科大学阜外心血管病医院冠心病研究室,北京100037 [3]延吉市卫生局疾病预防中心,吉林延吉133000

出　　处：《中国病理生理杂志》2008年第9期1665-1669,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30600240)

摘　　要：目的:探讨血管生成素-1(Ang-1)对人脐静脉内皮细胞(HUVECs)内游离镁离子浓度([Mg2+]i)的调节机制。方法:我们采用荧光指示剂mag-fura-2,运用PTi阳离子测定系统动态测HUVECs的[Mg2+]i。结果:Ang-1诱导的[Mg2+]i增加与细胞外Mg2+浓度无关。Ang-1诱导的[Mg2+]i增加与细胞内Ca2+浓度无关。经酪氨酸激酶阻断剂(tyrphostin A23和genistein),磷脂酰3激酶阻断剂(wortmannin和LY294002)预处理,均显著阻断Ang-1诱导的[Mg2+]i增加。但经活化丝裂原激活激酶阻断剂(SB202190和PD98059)预处理,不能阻断Ang-1诱导的[Mg2+]i增加。结论:Ang-1通过酪氨酸激酶/磷脂酰3激酶信号传递途径使细胞内的Mg2+库释放Mg2+,从而增加HUVECs的[Mg2+]i。AIM： The mechanism of angiopoietin - 1 （Ang - 1 ） in mediating increase in intracellular free magnesium （[ Mg^2＋]i） in human umbilical vein endothelial cells （HUVECs） was investigated in this study. METHODS： The change of [ Mg^2＋]i in HUVECs was quantitatively detected in intracellular cation measurement system via load- ed with the fluorescent magnesium indicator mag - fura - 2. RESULTS ： Ang - 1 increased [ Mg^2＋]i, and there was not any significant difference among the groups of 0 mmol/L and 1 mmol/L of extracellular Mg^2＋ . Similar results were obtained in groups done with Ca^2＋ . Pretreatment with tyrosine kinase inhibitors （ tyrphostin A23 and genistein）, phosphatidylinositol 3 -kinase （PI3K） inhibitors （wortmannin and LY294002） blocked the increase in [ Mg^2＋]i induced by Ang- 1. However, mitogen - activated protein kinase inhibitors （ SB202190 and PD98059 ） had no effect on the Ang - 1 - induced [ Mg2^2＋]i increase. CONCLUSION ： These results suggest that the increase in [ Mg^2＋]i by Ang - 1 come from intracellular Mg^2＋ pools mediated by tyrosine kinase/PDK -dependent signaling pathways.

关 键 词：血管生成素1 镁 酪氨酸激酶 1-磷脂酰肌醇3-激酶 

分 类 号：R363[医药卫生—病理学]