Different actions of cardioprotective agents on mitochondrial Ca2+ regulation in a Ca2+ paradox-induced Ca2+ overload.
Different actions of cardioprotective agents on mitochondrial Ca2+ regulation in a Ca2+ paradox-induced Ca2+ overload.
复制标题
在 Ca2 悖论诱导的 Ca2 超载中，心脏保护剂对线粒体 Ca2 调节的不同作用。
作者：
Masaki Matsunaga;M. Saotome;H. Satoh;H. Katoh;H. Terada;H. Hayashi
背景
线粒体Ca 2+超载是各种代谢应激过程中不可逆细胞损伤的主要原因。在大鼠心室肌细胞中研究了影响线粒体功能的各种药物对Ca 2+反常期间Ca 2+超载的保护作用。
方法和结果
在Ca ~（2+）耗竭后再补充Ca ~（2+）时，[Ca ~（2+）]i迅速升高，210个细胞中有90个（43%）死亡。在活细胞中，[Ca 2 +]i的增加低于死细胞。KB-R7943可抑制细胞内[Ca ~（2+）]i的升高，并完全抑制细胞死亡。钌红（RuR）、二氮嗪（Dz）或环孢菌素A（CsA）可防止细胞死亡（分别为15%、26%和17%; p < 0.05），而Dz的保护作用可被5-羟基癸酸消除。这些试剂没有降低活细胞中[Ca 2 +]i的增加或所有细胞中[Ca 2 +]i的初始增加速率。RuR和Dz降低去皮心肌细胞[Ca ~（2+）]m，CsA对[Ca ~（2+）]m无影响。Dz减少NADH荧光，而RuR和CsA没有。
结论
RuR和Dz的保护作用可归因于通过降低[Ca 2 +]m改变Ca 2+调节，并且Dz可对氧化磷酸化产生额外的作用。CsA的保护作用可能与线粒体通透性转换孔直接相关。
BACKGROUND
Mitochondrial Ca2+ overload is a major cause of irreversible cell injury during various metabolic stresses. The protective effects of various agents that affect mitochondrial function against Ca2+ overload during Ca2+ paradox were investigated in rat ventricular myocytes.
METHODS AND RESULTS
On Ca2+ repletion following Ca2+ depletion, [Ca2+]i increased rapidly, and 90 of 210 cells (43%) died. In viable cells, the increase in [Ca2+]i was lower than in dead cells. KB-R7943 prevented the increase in [Ca2+]i, and completely inhibited cell death. Ruthenium red (RuR), diazoxide (Dz) or cyclosporin A (CsA) prevented cell death (15%, 26% and 17%, respectively; p < 0.05), and the protective effect of Dz was abolished by 5-hydroxydecanoate. These agents did not reduce the increase in [Ca2+]i in viable cells or the rate of initial increase in [Ca2+]i in all cells. RuR and Dz decreased [Ca2+]m in skinned myocytes, but CsA did not affect [Ca2+]m. Dz reduced NADH fluorescence, whereas RuR and CsA did not.
CONCLUSIONS
The protective effects of RuR and Dz could be ascribed to altered Ca2+ regulation by decreasing [Ca2+]m, and Dz could have an additional effect on oxidative phosphorylation. The protective effect of CsA could be directly associated with the mitochondrial permeability transition pore.
DOI：
10.1152/ajpheart.00552.2001
发表时间：
2002-02-01
影响因子：
4.8
作者：
Ozcan, C;Bienengraeber, M;Terzic, A
通讯作者：
Terzic, A
影响因子：
37.8
作者：
Liu, YG;Sato, T;Marban, E
通讯作者：
Marban, E