Nitric oxide donors modulate ferritin and protect endothelium from oxidative injury.

Abstract

Ferritin protects endothelial cells from the damaging effects of iron-catalyzed oxidative injury. Regulation of ferritin occurs through the formation of an iron-sulfur cluster within a cytoplasmic protein, the iron regulatory protein (IRP) that controls ferritin mRNA translation. Nitric oxide has been shown to inhibit iron-sulfur proteins and is present at vascular sites of inflammation; therefore, we undertook a study to examine the influence of nitric oxide on changes in endothelial cell ferritin content in response to iron exposure, and the subsequent effects on susceptibility to oxidative injury. Iron-loaded endothelial cells (EC) exposed to nitric oxide donors synthesize markedly less ferritin. Treatment of EC with a nitric oxide donor increases IRP affinity for ferritin mRNA concomitant with a loss of cytoplasmic aconitase activity in iron-laden EC. Iron-treated EC exposed to NO donors were resistant to oxidative injury despite their low ferritin content when examined 1 h after the treatment period. In contrast, 24 h later, these same cells become sensitive to oxidants, whereas iron-treated EC that are ferritin-rich continue to be resistant. In conclusion, NO inhibits the increase of EC ferritin after exposure to iron but provides short-term protection against oxidants; ferritin, in turn, provides durable cytoprotection by inactivating reactive iron.

• Authors: M B Juckett, M Weber, J Balla, H S Jacob, G M Vercellotti
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 20 Issue 1 Pg. 63-73 ( 1996) ISSN: 0891-5849 [Print] United States
• PMID: 8903680 (Publication Type: Journal Article)

Chemical References

• DNA Probes
• Iron Compounds
• Iron-Regulatory Proteins
• Iron-Sulfur Proteins
• Polyamines
• RNA, Messenger
• RNA-Binding Proteins
• Vasodilator Agents
• diethylenetriamine
• Nitric Oxide
• Hemin
• S-Nitroso-N-Acetylpenicillamine
• Ferritins
• Heme Oxygenase (Decyclizing)
• Aconitate Hydratase
• Penicillamine

Topics

• Aconitate Hydratase (antagonists & inhibitors, metabolism)
• Animals
• Aorta (metabolism)
• Base Sequence
• Blotting, Northern
• Cells, Cultured
• DNA Probes (chemistry)
• Endothelium (metabolism)
• Ferritins (antagonists & inhibitors, metabolism)
• Heme Oxygenase (Decyclizing) (metabolism)
• Hemin (metabolism)
• Humans
• Iron Compounds (metabolism, pharmacology)
• Iron-Regulatory Proteins
• Iron-Sulfur Proteins (metabolism)
• Molecular Sequence Data
• Nitric Oxide (pharmacology)
• Oxidative Stress
• Penicillamine (analogs & derivatives, metabolism)
• Polyamines (metabolism)
• RNA, Messenger (metabolism)
• RNA-Binding Proteins (metabolism)
• S-Nitroso-N-Acetylpenicillamine
• Swine (metabolism)
• Umbilical Veins (metabolism)
• Vasodilator Agents (pharmacology)