caa a22 4500 445852658 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-010-0614-9 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0614-9 Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells [Elektronische Daten] [Patricia Tithof, Sean Richards, Mona Elgayyar, Fu-Minn Menn, Vijay Vulava, Larry McKay, John Sanseverino, Gary Sayler, Dawn Tucker, Christina Leslie, Kim Lu, Kenneth Ramos] 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 A2 (PLA2) 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 PLA2 in HCAECs, and activation of this enzyme was associated with histone fragmentation and poly (ADP) ribose polymerase (PARP) cleavage. Genetic silencing of group IVC PLA2 inhibited both 3H-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 PLA2. 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 PLA2. Springer-Verlag, 2010 Atherosclerosis nationallicence Lipid signaling nationallicence Phospholipase A2 nationallicence Apoptosis nationallicence Anthracene nationallicence Benzo(a)pyrene nationallicence Acenapthalene nationallicence Benzo(a)anthracene nationallicence Benzo(b)fluoranthene nationallicence Benzo(k)fluoranthene nationallicence Benzo(g, h, i)perylene nationallicence Tithof Patricia Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 37996-4545, Knoxville, TN, USA aut Richards Sean Department of Biological and Environmental Sciences, University of Tennessee, 37403, Chattanooga, TN, USA aut Elgayyar Mona Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 37996-4545, Knoxville, TN, USA aut Menn Fu-Minn Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut Vulava Vijay Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut McKay Larry Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut Sanseverino John Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut Sayler Gary Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut Tucker Dawn Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut Leslie Christina Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut Lu Kim Department of Biology, Texas A&M University, 77843, College Station, TX, USA aut Ramos Kenneth Department of Biochemistry and Molecular Biology, University of Louisville, 40202, Louisville, KY, USA aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 623-634 0340-5761 85:6<623 2011 85 204 https://doi.org/10.1007/s00204-010-0614-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0614-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tithof Patricia Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 37996-4545, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Richards Sean Department of Biological and Environmental Sciences, University of Tennessee, 37403, Chattanooga, TN, USA aut NATIONALLICENCE 700 1- Elgayyar Mona Department of Pathobiology, College of Veterinary Medicine, University of Tennessee, 37996-4545, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Menn Fu-Minn Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Vulava Vijay Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut NATIONALLICENCE 700 1- McKay Larry Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Sanseverino John Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Sayler Gary Center for Environmental Biotechnology, University of Tennessee, 37996, Knoxville, TN, USA aut NATIONALLICENCE 700 1- Tucker Dawn Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut NATIONALLICENCE 700 1- Leslie Christina Department of Pediatrics, National Jewish Medical and Research Center, 80206, Denver, CO, USA aut NATIONALLICENCE 700 1- Lu Kim Department of Biology, Texas A&M University, 77843, College Station, TX, USA aut NATIONALLICENCE 700 1- Ramos Kenneth Department of Biochemistry and Molecular Biology, University of Louisville, 40202, Louisville, KY, USA aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 623-634 0340-5761 85:6<623 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer