Ferritin: A cytoprotective antioxidant strategem of endothelium

G. Balla, Harry S. Jacob, J. Balla, Mark Rosenberg, Karl Nath, Fred Apple, John W. Eaton, Gregory M. Vercellotti

Research output: Contribution to journalArticle

874 Citations (Scopus)

Abstract

Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62 → Lys; His65 → Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.

Original languageEnglish
Pages (from-to)18148-18153
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number25
Publication statusPublished - Sep 5 1992

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Ferritins
Oxidants
Endothelium
Antioxidants
Endothelial cells
Apoferritins
Endothelial Cells
Heme Oxygenase (Decyclizing)
Cultured Cells
Iron
Iron Chelating Agents
Cytoplasmic Granules
Ceruloplasmin
Adult Respiratory Distress Syndrome
Vascular Endothelium
Cytotoxicity
Phagocytes
Heme
Hydrogen Peroxide
Lipid Peroxidation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Balla, G., Jacob, H. S., Balla, J., Rosenberg, M., Nath, K., Apple, F., ... Vercellotti, G. M. (1992). Ferritin: A cytoprotective antioxidant strategem of endothelium. Journal of Biological Chemistry, 267(25), 18148-18153.

Ferritin : A cytoprotective antioxidant strategem of endothelium. / Balla, G.; Jacob, Harry S.; Balla, J.; Rosenberg, Mark; Nath, Karl; Apple, Fred; Eaton, John W.; Vercellotti, Gregory M.

In: Journal of Biological Chemistry, Vol. 267, No. 25, 05.09.1992, p. 18148-18153.

Research output: Contribution to journalArticle

Balla, G, Jacob, HS, Balla, J, Rosenberg, M, Nath, K, Apple, F, Eaton, JW & Vercellotti, GM 1992, 'Ferritin: A cytoprotective antioxidant strategem of endothelium', Journal of Biological Chemistry, vol. 267, no. 25, pp. 18148-18153.
Balla G, Jacob HS, Balla J, Rosenberg M, Nath K, Apple F et al. Ferritin: A cytoprotective antioxidant strategem of endothelium. Journal of Biological Chemistry. 1992 Sep 5;267(25):18148-18153.
Balla, G. ; Jacob, Harry S. ; Balla, J. ; Rosenberg, Mark ; Nath, Karl ; Apple, Fred ; Eaton, John W. ; Vercellotti, Gregory M. / Ferritin : A cytoprotective antioxidant strategem of endothelium. In: Journal of Biological Chemistry. 1992 ; Vol. 267, No. 25. pp. 18148-18153.
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