Messmer U K, Reimer D M, Reed J C, Brüne B
University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV, Germany.
FEBS Lett. 1996 Apr 15;384(2):162-6. doi: 10.1016/0014-5793(96)00311-0.
Endogenously generated or exogenously supplied nitric oxide causes cleavage of poly(ADP-ribose) polymerase (PARP) and apoptotic cell death in RAW 264.7 macrophages. With the use of NO donors such as S-nitrosoglutathione or spermine-NO we established that PARP digestion occurs in parallel with DNA fragmentation, and is preceded by accumulation of the tumor suppressor gene product p53. PARP cleavage in response to lipopolysaccharide and interferon-gamma treatment is prevented by NG-monomethyl-L-arginine, thus proving a NO requirement. Endogenous NO generation, p53 accumulation, and PARP degradation occurred prior to the detection of significant chromatin condensation. In contrast, in stable Bcl-2 transfected cells, NO-initiated PARP cleavage was almost completely blocked. Our data implicate PARP as a proteolytic substrate during NO-mediated apoptotic cell death in RAW 264.7 macrophages and establish Bcl-2 as an efficient signal terminator in this process.
内源性生成或外源性供应的一氧化氮可导致聚（ADP - 核糖）聚合酶（PARP）裂解，并使RAW 264.7巨噬细胞发生凋亡性细胞死亡。使用诸如S - 亚硝基谷胱甘肽或精胺 - NO等一氧化氮供体，我们确定PARP消化与DNA片段化同时发生，并且在肿瘤抑制基因产物p53积累之前发生。NG - 单甲基 - L - 精氨酸可阻止脂多糖和干扰素 - γ处理引起的PARP裂解，从而证明需要一氧化氮。在检测到明显的染色质凝聚之前，就已发生内源性一氧化氮生成、p53积累和PARP降解。相反，在稳定转染Bcl - 2的细胞中，一氧化氮引发的PARP裂解几乎完全被阻断。我们的数据表明PARP是RAW 264.7巨噬细胞中一氧化氮介导的凋亡性细胞死亡过程中的蛋白水解底物，并确定Bcl - 2在此过程中是一种有效的信号终止剂。
