De Mello Walmor C
School of Medicine, University of Puerto Rico , San Juan, PR , USA.
Front Endocrinol (Lausanne). 2015 Jan 22;5:238. doi: 10.3389/fendo.2014.00238. eCollection 2014.
HighlightsIntracellular renin disrupts chemical communication in the heartAngiotensinogen enhances the effect of reninIntracellular enalaprilat reduces significantly the effect of reninIntracellular renin increases the inward calcium currentHarmful versus beneficial effect during myocardial infarction The influence of intracellular renin on the process of chemical communication between cardiac cells was investigated in cell pairs isolated from the left ventricle of adult Wistar Kyoto rats. The enzyme together with Lucifer yellow CH was dialyzed into one cell of the pair using the whole cell clamp technique. The diffusion of the dye in the dialyzed and in non-dialyzed cell was followed by measuring the intensity of fluorescence in both cells as a function of time. The results indicated that; (1) under normal conditions, Lucifer Yellow flows from cell to cell through gap junctions; (2) the intracellular dialysis of renin (100 nM) disrupts chemical communication - an effect enhanced by simultaneous administration of angiotensinogen (100 nM); (3) enalaprilat (10(-9) M) administered to the cytosol together with renin reduced drastically the uncoupling action of the enzyme; (4) aliskiren (10(-8) M) inhibited the effect of renin on chemical communication; (5) the possible role of intracellular renin independently of angiotensin II (Ang II) was evaluated including the increase of the inward calcium current elicited by the enzyme and the possible role of oxidative stress on the disruption of cell communication; (6) the possible harmful versus the beneficial effect of intracellular renin during myocardial infarction was discussed; (7) the present results indicate that intracellular renin due to internalization or in situ synthesis causes a severe impairment of chemical communication in the heart resulting in derangement of metabolic cooperation with serious consequences for heart function.
要点
细胞内肾素破坏心脏中的化学通讯
血管紧张素原增强肾素的作用
细胞内依那普利拉显著降低肾素的作用
细胞内肾素增加内向钙电流
心肌梗死期间的有害与有益作用
在从成年Wistar Kyoto大鼠左心室分离的细胞对中研究了细胞内肾素对心脏细胞间化学通讯过程的影响。使用全细胞钳技术将该酶与荧光黄CH一起透析到细胞对的一个细胞中。通过测量两个细胞中荧光强度随时间的变化来跟踪染料在透析细胞和未透析细胞中的扩散。结果表明：(1) 在正常条件下，荧光黄通过缝隙连接在细胞间流动；(2) 肾素（100 nM）的细胞内透析破坏化学通讯——同时给予血管紧张素原（100 nM）可增强此效应；(3) 与肾素一起给予细胞质的依那普利拉（10(-9) M）显著降低了该酶的解偶联作用；(4) 阿利吉仑（10(-8) M）抑制肾素对化学通讯的作用；(5) 评估了细胞内肾素独立于血管紧张素II（Ang II）的可能作用，包括该酶引起的内向钙电流增加以及氧化应激对细胞通讯破坏的可能作用；(6) 讨论了细胞内肾素在心肌梗死期间可能的有害与有益作用；(7) 目前的结果表明，由于内化或原位合成导致的细胞内肾素会严重损害心脏中的化学通讯，导致代谢合作紊乱，对心脏功能产生严重后果。
