Aspirin increases ferritin synthesis in endothelial cells: a novel antioxidant pathway.
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.
Oberle
S
S
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle (Saale), Germany.
Polte
T
T
Abate
A
A
Podhaisky
H P
HP
Schröder
H
H
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
D000975:Antioxidants; D012333:RNA, Messenger; D005293:Ferritins; D003676:Deferoxamine; D001241:Aspirin