Numata Tomohiro, Sato Kaori, Okada Yasunobu, Wehner Frank
Department of Cell Physiology, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki 444-8585, Japan.
Apoptosis. 2008 Jul;13(7):895-903. doi: 10.1007/s10495-008-0220-y.
Cell shrinkage is one of the earliest events during apoptosis. Cell shrinkage also occurs upon hypertonic stress, and previous work has shown that hypertonicity-induced cation channels (HICCs) underlie a highly efficient mechanism of recovery from cell shrinkage, called the regulatory volume increase (RVI), in many cell types. Here, the effects of HICC activation on staurosporine-induced apoptotic volume decrease (AVD) and apoptosis were studied in HeLa cells by means of electronic cell sizing and whole-cell patch-clamp recording. It was found that hypertonic stress reduces staurosporine-induced AVD and cell death (associated with caspase-3/7 activation and DNA fragmentation), and that this effect was actually due to activation of the HICC. On the other hand, staurosporine was found to significantly reduce osmotic HICC activation. It is concluded that AVD and RVI reflect two fundamentally distinct functional modes in terms of the activity and role of the HICC, in a shrunken cell. Our results also demonstrate, for the first time, the ability of the HICC to rescue cells from the process of programmed cell death.
细胞皱缩是细胞凋亡过程中最早出现的事件之一。在高渗应激时也会发生细胞皱缩，先前的研究表明，在许多细胞类型中，高渗诱导的阳离子通道（HICCs）是一种从细胞皱缩中恢复的高效机制的基础，这种机制称为调节性容积增加（RVI）。在此，通过电子细胞大小测定和全细胞膜片钳记录，研究了HICC激活对HeLa细胞中星形孢菌素诱导的凋亡性容积减小（AVD）和细胞凋亡的影响。研究发现，高渗应激可减少星形孢菌素诱导的AVD和细胞死亡（与半胱天冬酶-3/7激活和DNA片段化相关），而这种效应实际上是由于HICC的激活所致。另一方面，发现星形孢菌素可显著降低渗透性HICC激活。可以得出结论，就HICC在皱缩细胞中的活性和作用而言，AVD和RVI反映了两种根本不同的功能模式。我们的结果还首次证明了HICC能够将细胞从程序性细胞死亡过程中拯救出来。
