Kluck R M, McDougall C A, Harmon B V, Halliday J W
Liver Unit, Queensland Institute of Medical Research, Herston, Brisbane, Australia.
Biochim Biophys Acta. 1994 Sep 8;1223(2):247-54. doi: 10.1016/0167-4889(94)90233-x.
A moderate sustained rise in intracellular ionised calcium has been observed to be associated with apoptosis occurring in many experimental systems. The application of extracellular and intracellular chelators of calcium has been reported to produce a decrease in apoptosis, while the addition of calcium ionophores often increases apoptosis. These findings, together with the observation of calcium-induced internucleosomal DNA cleavage in isolated nuclei, have suggested that DNA cleavage (and apoptosis) is a calcium-dependent process. However, a number of studies have shown that apoptosis is not always associated with a rise in the level of intracellular ionised calcium. In the present study, calcium chelators were found to induce apoptosis in cultured cells, concomitant with a decrease in both intracellular ionised calcium and total cell calcium content. Decreased intracellular ionised magnesium was also induced by extracellular chelators. These findings provide further evidence that a raised intracellular ionised calcium is not universally present during the induction of apoptosis. It is proposed that loss of calcium homeostasis, rather than a sustained rise in cytosolic calcium, is a determining factor in cell death by apoptosis.
在许多实验系统中，已观察到细胞内游离钙的适度持续升高与凋亡相关。据报道，应用细胞外和细胞内钙螯合剂可使凋亡减少，而添加钙离子载体通常会增加凋亡。这些发现，连同在分离细胞核中观察到钙诱导的核小体间DNA裂解，提示DNA裂解（及凋亡）是一个钙依赖性过程。然而，多项研究表明，凋亡并不总是与细胞内游离钙水平升高相关。在本研究中，发现钙螯合剂可诱导培养细胞凋亡，同时细胞内游离钙和细胞总钙含量均降低。细胞外螯合剂也可诱导细胞内游离镁减少。这些发现进一步证明，在凋亡诱导过程中，细胞内游离钙升高并非普遍存在。有人提出，钙稳态的丧失，而非胞质钙的持续升高，是细胞凋亡性死亡的决定因素。
