Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996-4545, USA.
Arch Toxicol. 2011 Jun;85(6):623-34. doi: 10.1007/s00204-010-0614-9. Epub 2010 Dec 4.
Exposure to environmental pollutants, such as polycyclic aromatic hydrocarbons (PAHs) found in coal tar mixtures and tobacco sources, is considered a significant risk factor for the development of heart disease in humans. The goal of this study was to determine the influence of PAHs present at a Superfund site on human coronary artery endothelial cell (HCAEC) phospholipase A(2) (PLA(2)) activity and apoptosis. Extremely high levels of 12 out of 15 EPA high-priority PAHs were present in both the streambed and floodplain sediments at a site where an urban creek and its adjacent floodplain were extensively contaminated by PAHs and other coal tar compounds. Nine of the 12 compounds and a coal tar mixture (SRM 1597A) activated group IVC PLA(2) in HCAECs, and activation of this enzyme was associated with histone fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Genetic silencing of group IVC PLA(2) inhibited both (3)H-fatty acid release and histone fragmentation by PAHs and SRM 1597A, indicating that individual PAHs and a coal tar mixture induce apoptosis of HCAECs via a mechanism that involves group IVC PLA(2). Western blot analysis of aortas isolated from feral mice (Peromyscus leucopus) inhabiting the Superfund site showed increased PARP and caspase-3 cleavage when compared to reference mice. These data suggest that PAHs induce apoptosis of HCAECs via activation of group IVC PLA(2).
暴露于环境污染物，如煤焦油混合物和烟草来源中的多环芳烃（PAHs），被认为是人类心脏病发展的重要危险因素。本研究的目的是确定超级基金场址中存在的 PAHs 对人冠状动脉内皮细胞（HCAEC）磷脂酶 A（PLA）（2）（PLA（2））活性和细胞凋亡的影响。在一个城市溪流及其相邻洪泛区被 PAHs 和其他煤焦油化合物广泛污染的地点，河床和洪泛区沉积物中存在 15 种 EPA 优先 PAHs 中的 12 种，其浓度极高。这 12 种化合物中的 9 种和煤焦油混合物（SRM 1597A）激活了 HCAEC 中的 IV 组 PLA（2），并且这种酶的激活与组蛋白片段化和多（ADP）核糖聚合酶（PARP）裂解有关。IV 组 PLA（2）的基因沉默抑制了 PAHs 和 SRM 1597A 诱导的（3）H-脂肪酸释放和组蛋白片段化，表明单独的 PAHs 和煤焦油混合物通过涉及 IV 组 PLA（2）的机制诱导 HCAEC 细胞凋亡。从栖息在超级基金场地上的野生老鼠（Peromyscus leucopus）分离的主动脉的 Western blot 分析表明，与参考老鼠相比，PARP 和 caspase-3 的切割增加。这些数据表明，PAHs 通过激活 IV 组 PLA（2）诱导 HCAEC 细胞凋亡。
