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

Stefanie Oberle, Petra Schwartz, Aida Abate, Henning Schröder

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

The organic nitrate pentaerithrityl tetranitrate (PETN) is known to exert long-term antioxidant and antiatherogenic effects by as yet unidentified mechanisms. In porcine aortic endothelial cells, a 24 h incubation with PETN (1-100 μM) or its metabolite pentaerithrityl trinitrate (PETriN) increased levels of the antioxidant protein ferritin up to three-fold over basal, whereas isosorbide dinitrate and isosorbide-5-mononitrate were without significant 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 dibutyryl cyclic GMP did not influence basal ferritin synthesis. The iron chelator desferrioxamine abolished ferritin induction by PETriN. Our results show that PETN or its active metabolite PETriN induce ferritin synthesis through NO- and iron-dependent but cyclic GMP-independent pathways. Increased activity of ferritin may contribute to, and at least in part explain, the specific antiatherogenic and antioxidant action of PETN.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume261
Issue number1
DOIs
StatePublished - Jul 22 1999
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Deutsche Forschungsgemein-schaft (Schr 298/8-2).

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