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 I 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.
Original language | English (US) |
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Pages (from-to) | 63-73 |
Number of pages | 11 |
Journal | Free Radical Biology and Medicine |
Volume | 20 |
Issue number | 1 |
DOIs | |
State | Published - 1996 |
Keywords
- Endothelium
- Ferritin
- Free radicals
- Nitric oxide
- Oxidative injury