Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells

Patricia K. Tithof, Sean M. Richards, Mona A. Elgayyar, Fu Minn Menn, Vijay M. Vulava, Larry McKay, John Sanseverino, Gary Sayler, Dawn E. Tucker, Christina C. Leslie, Kim P. Lu, Kenneth S. Ramos

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)623-634
Number of pages12
JournalArchives of Toxicology
Volume85
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Keywords

  • Acenapthalene
  • Anthracene
  • Apoptosis
  • Atherosclerosis
  • Benzo(a)anthracene
  • Benzo(a)pyrene
  • Benzo(b)fluoranthene
  • Benzo(g, h, i)perylene
  • Benzo(k)fluoranthene
  • Lipid signaling
  • Phospholipase A

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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  • Cite this

    Tithof, P. K., Richards, S. M., Elgayyar, M. A., Menn, F. M., Vulava, V. M., McKay, L., Sanseverino, J., Sayler, G., Tucker, D. E., Leslie, C. C., Lu, K. P., & Ramos, K. S. (2011). Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells. Archives of Toxicology, 85(6), 623-634. https://doi.org/10.1007/s00204-010-0614-9