Aspirin increases ferritin synthesis in endothelial cells: A novel antioxidant pathway

Stefanie Oberle, Tobias Polte, Aida Abate, Hans Peter Podhaisky, Henning Schröder

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Aspirin has recently been shown to increase endothelial resistance to oxidative damage. However, the mechanism underlying aspirin-induced cytoprotection is still unknown. Using cultured cells, the present study investigates the effect of aspirin on the expression of ferritin, a cytoprotective protein that sequesters free cytosolic iron, the main catalyst of oxygen radical formation. In bovine pulmonary artery endothelial cells, aspirin at low antithrombotic concentrations (0.03 to 0.3 mmol/L) induced the synthesis of ferritin protein in a time- and concentration-dependent fashion up to 5-fold over basal levels, whereas ferritin H (heavy chain) mRNA remained unaltered. Aspirin-induced cytoprotection from hydrogen peroxide toxicity was mimicked by exogenous iron-free apoferritin but not iron-loaded ferritin, demonstrating the antioxidant function of newly synthesized ferritin under these conditions. Ferritin induction by aspirin was specific in that other nonsteroidal anti-inflammatory drugs such as salicylic acid, indomethacin, or diclofenac failed to alter ferritin protein levels. Aspirin- induced ferritin synthesis was abrogated in the presence of the iron chelator desferrioxamine, pointing to an interaction of aspirin with iron-responsive activation of ferritin translation. Together, our results suggest induction of ferritin as a novel mechanism by which aspirin may prevent endothelial injury in cardiovascular disease, eg, during atherogenesis.

Original languageEnglish (US)
Pages (from-to)1016-1020
Number of pages5
JournalCirculation research
Volume82
Issue number9
DOIs
StatePublished - May 18 1998

Keywords

  • Antioxidant defense mechanism
  • Aspirin
  • Endothelial cell
  • Ferritin
  • Gene expression

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