title: Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway.
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.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle (Saale), Germany.
authors.forename: S
authors.initials: S
authors.lastname: Oberle
authors.forename: T
authors.initials: T
authors.lastname: Polte
authors.forename: A
authors.initials: A
authors.lastname: Abate
authors.forename: H P
authors.initials: HP
authors.lastname: Podhaisky
authors.forename: H
authors.initials: H
authors.lastname: Schröder
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005293:Ferritins / Q000096:biosynthesis*; D015870:Gene Expression / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D000975:Antioxidants; D012333:RNA, Messenger; D005293:Ferritins; D003676:Deferoxamine; D001241:Aspirin