Staurosporine-induced cell death in salmonid cells: the role of apoptotic volume decrease, ion fluxes and MAP kinase signaling
Staurosporine-induced cell death in salmonid cells: the role of apoptotic volume decrease, ion fluxes and MAP kinase signaling
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DOI：
10.1007/s10495-007-0103-7
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发表时间：
2007-10-01
期刊：
影响因子：
7.2
通讯作者：
Manzl, Claudia
中科院分区：
文献类型：
--
作者：
Krumschnabel, Gerhard;Maehr, Tanja;Manzl, Claudia
哺乳动物模型中的细胞凋亡通常与细胞皱缩有关。抑制凋亡体积减少（AVD）具有细胞保护作用，表明细胞皱缩是凋亡中重要的早期事件。在鲑鱼肝癌和鳃细胞星形孢菌素诱导细胞凋亡，作为评估的效应半胱天冬酶，核凝聚，和线粒体膜电位（MMP）的降低，激活，这些变化伴随着细胞皱缩。Cl-转运抑制剂DIDS和K+通道抑制剂奎尼丁可防止AVD，但只有DIDS抑制凋亡。其他Cl-通量抑制剂以及泛半胱天冬酶抑制剂不能防止细胞收缩，但仍能防止半胱天冬酶活化。此外，在低渗条件下，调节性容积减少（RVD）并不容易，但减少了凋亡细胞。由于所有的转运抑制剂都能阻断RVD，但只有DIDS和奎尼丁能抑制AVD，因此参与这两个过程的离子转运蛋白显然是不同的。此外，我们的数据表明，抑制Cl（-）流量，而不是阻止细胞收缩或K（+）流量是重要的，以防止凋亡。与此一致，抑制MAP激酶降低了RVD而非AVD，但仍降低了半胱天冬酶活化。最后，我们观察到MAP激酶在星形孢菌素处理后被激活，并且当AVD被抑制时，至少ERK的激活被阻止。
Apoptotic cell death in mammalian models is frequently associated with cell shrinkage. Inhibition of apoptotic volume decrease (AVD) is cytoprotective, suggesting that cell shrinkage is an important early event in apoptosis. In salmonid hepatoma and gill cells stauro-sporine induced apoptosis, as assessed by activation of effector caspases, nuclear condensation, and a decrease of mitochondrial membrane potential (MMP), and these changes were accompanied by cell shrinkage. The Cl(-) transport inhibitor DIDS and the K(+) channel inhibitor quinidine prevented AVD, but only DIDS inhibited apoptosis. Other Cl- flux inhibitors, as well as a pan-caspase inhibitor, did not prevent cell shrinkage, but still prevented caspase activation. Furthermore, regulatory volume decrease (RVD) under hypotonic conditions was not facilitated, but diminished in apoptotic cells. Since all transport inhibitors used blocked RVD, but only DIDS and quinidine inhibited AVD, the ion transporters involved in both processes are apparently not identical. In addition, our data indicate that inhibition of Cl(-) fluxes rather than blocking cell shrinkage or K(+) fluxes is important for preventing apoptosis. In line with this, inhibition of MAP kinases reduced RVD and not AVD, but still diminished caspase activation. Finally, we observed that MAP kinases were activated upon staurosporine treatment and that at least activation of ERK was prevented when AVD was inhibited.