Hwang S G, Lee H C, Lee D W, Kim Y S, Joo W H, Cho Y K, Moon J Y
Department of Biochemistry and Health Sciences, College of Natural Sciences, Changwon National University, Changwon, 641-773, Kyungnam, South Korea.
Toxicology. 2001 Aug 28;165(2-3):179-88. doi: 10.1016/s0300-483x(01)00432-2.
Apoptotic cell death is an active process, which is a critical feature of the regulated development of multicellular organisms. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. This study investigates the 2,2', 5,5'-tetrachlorobiphenyl (PCB 52) induced apoptosis in human neuronal SK-N-MC cells, and the role of p53 in this response. Upon treatments with PCB 52, time- and concentration-dependent inhibition of the cell viability was observed. PCB 52 also caused apoptosis, as measured by cell morphology and DNA fragmentation. The capability of PCB 52 to induce apoptosis was associated with the proteolytic cleavage of specific target proteins, such as poly(ADP-ribose) polymerase (PARP) and beta-catenin proteins, suggesting the possible involvement of caspases. In general, DNA-damaging agents induce accumulation of the tumor suppressor protein p53, leading cells to either growth arrest in G1, or apoptosis. However, our data showed that both p53 and Bcl-2 protein levels were decreased in a time-dependent manner during apoptosis after exposure to PCB 52. These results suggest that PCB 52 induced a p53-independent apoptosis in these cells.
凋亡性细胞死亡是一个活跃的过程，是多细胞生物体调控发育的关键特征。多氯联苯（PCBs）是普遍存在的环境污染物，其中一些可能具有神经毒性。本研究调查了2,2',5,5'-四氯联苯（PCB 52）诱导人神经母细胞瘤SK-N-MC细胞凋亡的情况，以及p53在这一反应中的作用。在用PCB 52处理后，观察到细胞活力呈时间和浓度依赖性抑制。PCB 52还导致了细胞凋亡，这通过细胞形态和DNA片段化来衡量。PCB 52诱导凋亡的能力与特定靶蛋白如聚（ADP-核糖）聚合酶（PARP）和β-连环蛋白的蛋白水解切割有关，这表明半胱天冬酶可能参与其中。一般来说，DNA损伤剂会诱导肿瘤抑制蛋白p53的积累，导致细胞在G1期生长停滞或凋亡。然而，我们的数据显示，在暴露于PCB 52后的凋亡过程中，p53和Bcl-2蛋白水平均呈时间依赖性下降。这些结果表明，PCB 52在这些细胞中诱导了一种不依赖p53的凋亡。
