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Ferritin: a cytoprotective antioxidant strategem of endothelium.

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Balla, G, Jacob, H.S., Balla, J, Rosenberg, M, Nath, K, Apple, F, Eaton, J.W., Vercellotti, G.M.·1992·Journal of Biological Chemistry

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.

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Metadata

Authors
Balla, G., Jacob, H. S., Balla, J., Rosenberg, M., Nath, K., Apple, F., Eaton, J. W., & Vercellotti, G. M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1992-09
Volume
267
Issue
25
Pages
18148-18153
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1621595817
Cited by
1,097
References
0
FWCI
5.85
Type
journal article
Language
en
Open access
hybrid
Licence

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