Low levels of arsenic trioxide stimulate proliferative signals in primary vascular cells without activating stress effector pathways

Aaron Barchowsky*, Robert R. Roussel, Linda R. Klei, Philip E. James, Neema Ganju, Karol R. Smith, Edward J. Dudek

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

172 Citations (Scopus)

Abstract

Chronic human exposure to low levels of inorganic arsenic increases the incidence of vascular diseases and specific cancers. Exposure of endothelial cells to environmentally relevant concentrations of arsenic trioxide (arsenite) induces oxidant formation, activates the transcription factor NF- κB, and increases DNA synthesis (Barchowsky et al., Free Radic. Biol. Med. 21, 783-790, 1996). We show, in the current study, that arsenite induces concentration-dependent cell proliferation or death in primary porcine aortic endothelial cells. Low concentrations caused cell proliferation and were associated with increased superoxide and H2O2 accumulation, cSrc activity, H2O2-dependent tyrosine phosphorylation, and NF-κB-dependent transcription. These concentrations were insufficient to activate MAP kinases. However, the MAP kinases, extracellular signal-regulated kinase and p38, were activated in response to levels of arsenite that caused cell death. These data suggest that arsenite-induced oxidant accumulation and subsequent activation of tyrosine phosphorylation represent a MAPK-independent pathway for phenotypic change and proliferation in vascular cells.

Original languageEnglish
Pages (from-to)65-75
Number of pages11
JournalToxicology and Applied Pharmacology
Volume159
Issue number1
DOIs
Publication statusPublished - 15 Aug 1999
Externally publishedYes

Keywords

  • Arsenic
  • Arsenite
  • Endothelial cells
  • Erk
  • Hydrogen peroxide
  • Mitogen-activated kinase
  • NF-κB
  • Oxidant stress
  • Src kinase
  • p38

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