Excitation-contraction coupling in ventricular myocytes is enhanced by paracrine signaling from mesenchymal stem cells.
Excitation-contraction coupling in ventricular myocytes is enhanced by paracrine signaling from mesenchymal stem cells.
复制标题
DOI：
10.1016/j.yjmcc.2012.03.008
复制
发表时间：
2012-06
影响因子：
5
通讯作者：
Banach K
中科院分区：
文献类型：
--
作者：
DeSantiago J;Bare DJ;Semenov I;Minshall RD;Geenen DL;Wolska BM;Banach K
在临床试验中，将间充质干细胞（MSC）移植到心脏缺血区域以减少梗死面积并改善收缩力。然而，MSC介导的心脏保护的机制和时间过程还不完全清楚。我们测试了MSC的旁分泌信号促进心脏兴奋-收缩（EC）偶联的变化，保护心肌细胞免于细胞死亡并增强收缩力的假设。分离的小鼠心室肌细胞（VM）用对照酪氨酸、MSC条件酪氨酸（ConT）处理或与MSC共培养。VM的钙处理性能通过激光扫描共聚焦显微镜和全细胞电压钳进行监测。VM的ConT灌流导致Ca瞬时振幅的时间依赖性增加（ConT 15 min：ΔF/F0=3.52±0.38，n=14; Ctrl 15 min：ΔF/F0=2.41±0.35，n=14）和Ca瞬时衰减的加速（τ：ConT：269±18 ms n=14; vs. Ctrl：315±57 ms，n=14）。电压钳记录证实了ConT诱导的伊卡，L增加（ConT：−5.9±0.5 pA/pF，n=11;对比对照：−4.04±0.3 pA/pF，n=12）。τ的变化是由于SERCA活性增加所致。PI 3 K抑制剂Wortmannin（100 nmol/L）和LY 294002（10 μmol/L）以及Akt抑制剂V（20 μmol/L）可抑制Ca瞬时振幅和τ的变化，表明其通过PI 3 K信号转导和Akt激活进行调节。在eNOS−/−心肌细胞中，τ的变化也被阻止，或者通过抑制eNOS来阻止τ的变化，这表明NO介导的SERCA活性调节。由于旁分泌信号进一步导致VM存活增加，我们提出Akt诱导的Ca信号变化也是MSC介导抗凋亡作用的机制。
In clinical trials mesenchymal stem cells (MSCs) are transplanted into cardiac ischemic regions to decrease infarct size and improve contractility. However, the mechanism and time course of MSC-mediated cardioprotection are incompletely understood. We tested the hypothesis that paracrine signaling by MSCs promotes changes in cardiac excitation-contraction (EC) coupling that protects myocytes from cell death and enhances contractility. Isolated mouse ventricular myocytes (VMs) were treated with control tyrode, MSC conditioned-tyrode (ConT) or co-cultured with MSCs. The Ca handling properties of VMs were monitored by laser scanning confocal microscopy and whole cell voltage clamp. ConT superfusion of VMs resulted in a time dependent increase of the Ca transient amplitude (ConT15min: ΔF/F0=3.52±0.38, n=14; Ctrl15min: ΔF/F0=2.41±0.35, n=14) and acceleration of the Ca transient decay (τ: ConT: 269±18 ms n=14; vs. Ctrl: 315±57 ms, n=14). Voltage clamp recordings confirmed a ConT induced increase in ICa,L (ConT: −5.9±0.5 pA/pF n=11; vs. Ctrl: −4.04±0.3 pA/pF, n=12). The change of τ resulted from increased SERCA activity. Changes in the Ca transient amplitude and τ were prevented by the PI3K inhibitors Wortmannin (100 nmol/L) and LY294002 (10 μmol/L) and the Akt inhibitor V (20 μmol/L) indicating regulation through PI3K signal transduction and Akt activation which was confirmed by western blotting. A change in τ was also prevented in eNOS−/− myocytes or by inhibition of eNOS suggesting an NO mediated regulation of SERCA activity. Since paracrine signaling further resulted in increased survival of VMs we propose that the Akt induced change in Ca signaling is also a mechanism by which MSCs mediate an anti-apoptotic effect.
登录
查看更多内容
AKT通过调节Cavalpha1蛋白稳定性来调节L型Ca2+通道活性。
DOI：
10.1083/jcb.200805063
发表时间：
2009-03-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Catalucci D;Zhang DH;DeSantiago J;Aimond F;Barbara G;Chemin J;Bonci D;Picht E;Rusconi F;Dalton ND;Peterson KL;Richard S;Bers DM;Brown JH;Condorelli G
通讯作者：
Condorelli G
影响因子：
10.8
作者：
Kinugawa, S;Tsutsui, H;Takeshita, A
通讯作者：
Takeshita, A
影响因子：
5
作者：
Lai, Ruenn Chai;Arslan, Fatih;Lim, Sai Kiang
通讯作者：
Lim, Sai Kiang
影响因子：
37.8
作者：
Chang, MG;Tung, L;Abraham, R
通讯作者：
Abraham, R
影响因子：
5
作者：
Dai, Ying;Ashraf, Muhammad;Xu, Meifeng
通讯作者：
Xu, Meifeng