CDD：细胞内钾离子抑制细胞凋亡的机制的新发现

生物谷

生物谷报道：细胞内离子对调控细胞凋亡与生长具有极其重要的意义，如细胞内钙离子直接调控细胞生长与凋亡，钙的不足会影响细胞的运动与生长，但钙离子浓度过高，如钙超载情况则会引起细胞凋亡的发生。而对其它离子与细胞生长和凋亡的研究相对较少，如K+，Cl-等。中国科学院神经所王以政研究员在此方面做了大量研究，证明在神经元内，K+离子是调控细胞凋亡的最关键因素之一，并有相关文章发表。最近在Nature系列杂志之一的Cell death & differentiation发表了韩国学者的文章，细胞内K+离子调控细胞凋亡的机制，与Apaf-1有关，而不是与Cyt-C相关，这揭示细胞内离子调控细胞生长发育与凋亡的机制提供了新的线索。

原始文献：

Intracellular K⁺ inhibits apoptosis by suppressing the Apaf-1 apoptosome formation and subsequent downstream pathways but not cytochrome c release

P Karki, C Seong, J-E Kim, K Hur, S Y Shin, J S Lee, B Cho and I-S Park

Cell Death Differ 14: 2068-2075; advance online publication, September 21, 2007; doi:10.1038/sj.cdd.4402221

Cellular ionic homeostasis, fundamentally K⁺ homeostasis, has been implicated as a critical regulator of apoptosis. The intracellular K⁺ efflux on apoptotic insult and suppression of apoptosis by high concentration of extracellular K⁺ or after inhibition of this efflux by K⁺ channel blockers have established the crucial role of K⁺ in turning on the apoptotic machinery. Several contrasting observations have reported the antiapoptotic effect of intracellular K⁺ concentration to be the result of inhibition of cytochrome c release from mitochondria, but the exact inhibitory mechanism remains obscure. However, here we show the blockage of K⁺ efflux during apoptosis did not affect cytochrome c release from the mitochondria, still completely inhibited the formation of the apoptosome comprising Apaf-1, cytochrome c, caspase-9 and other accessories. As a consequence of this event, procaspase-9, -3, -8 and other death-related proteins were not processed. Furthermore, physiological concentrations of K⁺ also inhibited the processing of procaspase-3 by purified caspase-8 or -9, the nucleosomal DNA fragmentation by purified DFF40/CAD and the nuclear fragmentation to varying extents. Altogether, these findings suggest that the efflux of K⁺ is prerequisite not only for the formation of the apoptosome but also for the downstream apoptotic signal-transduction pathways.