Nitric oxide donors modulate ferritin and protect endothelium from oxidative injury

Mark B. Juckett, Marc Weber, József Balla, Harry S Jacob, Gregory M Vercellotti

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 languageEnglish (US)
Pages (from-to)63-73
Number of pages11
JournalFree Radical Biology and Medicine
Volume20
Issue number1
DOIs
StatePublished - Jan 1 1996

Keywords

  • Endothelium
  • Ferritin
  • Free radicals
  • Nitric oxide
  • Oxidative injury

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