The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells

The organic nitrate pentaerithrityl tetranitrate (PETN) is known to exert l ong-term antioxidant and antiatherogenic effects by as yet unidentified mec hanisms. In porcine aortic endothelial cells, a 24 h incubation with PETN ( 1-100 mu M) or its metabolite pentaerithrityl trinitrate (PETriN) increased levels of the antioxidant protein ferritin up to three-fold over basal, wh ereas isosorbide dinitrate and isosorbide-5-mononitrate were without signif icant effect under these conditions. PETriN-induced ferritin expression was blocked by the NO scavenger PTIO but remained unaltered in the presence of ODQ, an inhibitor of soluble guanylyl cyclase. 8-Bromo cyclic GMP and dibu tyryl cyclic GMP did not influence basal ferritin synthesis. The iron chlel ator desferrioxamine abolished ferritin induction by PETriN. Our results sh ow that PETN or its active metabolite PETriN induce ferritin synthesis thro ugh NO- and iron-dependent but cyclic GMP-independent pathways. Increased a ctivity of ferritin may contribute to, and at least in part explain, the sp ecific antiatherogenic and antioxidant action of PETN. (C) 1999 Academic Pr ess.