Leist M, Single B, Künstle G, Volbracht C, Hentze H, Nicotera P
Department of Molecular Toxicology, University of Konstanz, Germany.
Biochem Biophys Res Commun. 1997 Apr 17;233(2):518-22. doi: 10.1006/bbrc.1997.6491.
Cleavage of poly-(ADP-ribose) polymerase is a process occurring early during the execution phase of apoptosis. Although in many experimental systems PARP cleavage indicates a point of no return, the significance of this proteolytic step for apoptosis remains unclear. Here we compare the susceptibility of cells from wild-type mice and PARP-/- mice to several inducers of apoptosis. Neither the susceptibility of hepatocytes towards CD95 or TNF-mediated apoptosis nor the activation of PARP-cleaving caspases was modified in PARP-/- liver cells. Thymocytes with either genotype exhibited similar sensitivity to treatments with ceramide, dexamethasone, or etoposide. The sensitivity of primary neurons towards apoptosis induced by staurosporine, colchicine, potassium withdrawal, peroxynitrite, or the neurotoxin MPP+ was also unaltered. These data suggest that neither activation nor cleavage of PARP has a causal role in apoptotic cell death of primary, non-transformed cells.
聚（ADP - 核糖）聚合酶的裂解是细胞凋亡执行阶段早期发生的一个过程。尽管在许多实验系统中，PARP裂解表明细胞已进入不可逆阶段，但这一蛋白水解步骤在细胞凋亡中的意义仍不清楚。在此，我们比较了野生型小鼠和PARP基因敲除小鼠的细胞对几种凋亡诱导剂的敏感性。在PARP基因敲除的肝细胞中，肝细胞对CD95或TNF介导的凋亡的敏感性以及PARP裂解半胱天冬酶的激活均未改变。两种基因型的胸腺细胞对神经酰胺、地塞米松或依托泊苷处理的敏感性相似。原代神经元对星形孢菌素、秋水仙碱、钾离子去除、过氧亚硝酸盐或神经毒素MPP +诱导的凋亡的敏感性也未改变。这些数据表明，PARP的激活或裂解在原代未转化细胞的凋亡性细胞死亡中均无因果作用。
