Counis Marie-France, Torriglia Alicia
INSERM U 598, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Biochimie. 2006 Dec;88(12):1851-8. doi: 10.1016/j.biochi.2006.07.008. Epub 2006 Aug 8.
Apoptosis is characterized by cell shrinkage, nuclear condensation and internucleosomal DNA cleavage. Besides the central role of caspases and other proteases, cell death triggers DNA degradation so that DNases have an active role in apoptotic cell death. The best-characterized apoptotic DNase is CAD, a neutral Mg-dependent endonuclease. Its activity is regulated by its inhibitor, ICAD, which is cleaved by caspases. Other neutral DNases have been shown to cleave nuclear DNA in apoptotic conditions: endonuclease G, GADD. In cells, the cytosolic pH is maintained to 7.2, mostly due to the activity of the Na(+)/H(+) exchanger. In many apoptotic conditions, a decrease of the intracellular pH has been shown. This decrease may activate different acid DNases, mostly when pH decreases below 6.5. Three acidic DNases II are so far known: DNase II alpha, DNase II beta and L-DNase II, a DNase II, derived from the serpin LEI (Leukocyte Elastase Inhibitor). Their activation during cell death is discussed in this review.
细胞凋亡的特征是细胞萎缩、核浓缩和核小体间DNA裂解。除了半胱天冬酶和其他蛋白酶的核心作用外，细胞死亡还会引发DNA降解，因此脱氧核糖核酸酶在凋亡性细胞死亡中发挥着积极作用。最具特征的凋亡脱氧核糖核酸酶是CAD，一种依赖镁的中性内切核酸酶。其活性受其抑制剂ICAD调节，ICAD会被半胱天冬酶切割。其他中性脱氧核糖核酸酶已被证明在凋亡条件下可切割核DNA：内切核酸酶G、GADD。在细胞中，胞质pH值维持在7.2，这主要归因于Na(+)/H(+)交换体的活性。在许多凋亡条件下，细胞内pH值已被证明会降低。这种降低可能会激活不同的酸性脱氧核糖核酸酶，尤其是当pH值降至6.5以下时。目前已知三种酸性脱氧核糖核酸酶II：脱氧核糖核酸酶IIα、脱氧核糖核酸酶IIβ和L-脱氧核糖核酸酶II，一种源自丝氨酸蛋白酶抑制剂LEI（白细胞弹性蛋白酶抑制剂）的脱氧核糖核酸酶II。本文综述了它们在细胞死亡过程中的激活情况。
