Endothelial cell heme oxygenase and ferritin induction by heme proteins

a possible mechanism limiting shock damage.

J. Balla, H. S. Jacob, G. Balla, K. Nath, G. M. Vercellotti

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalTransactions of the Association of American Physicians
Volume105
Publication statusPublished - 1992

Fingerprint

Hemeproteins
Heme Oxygenase (Decyclizing)
Methemoglobin
Shock
Heme
Endothelial Cells
Hemopexin
Oxidants
Hemin
Hemoglobins
Haptoglobins
Endothelium
Sodium Cyanide
Metmyoglobin
Disseminated Intravascular Coagulation
Endothelins
Ferritins
Cytochromes c
Blood Vessels
haemoferritin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Endothelial cell heme oxygenase and ferritin induction by heme proteins : a possible mechanism limiting shock damage. / Balla, J.; Jacob, H. S.; Balla, G.; Nath, K.; Vercellotti, G. M.

In: Transactions of the Association of American Physicians, Vol. 105, 1992, p. 1-6.

Research output: Contribution to journalArticle

@article{ac1ffbdcc1674768894bdd15eaa16e13,
title = "Endothelial cell heme oxygenase and ferritin induction by heme proteins: a possible mechanism limiting shock damage.",
abstract = "Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.",
author = "J. Balla and Jacob, {H. S.} and G. Balla and K. Nath and Vercellotti, {G. M.}",
year = "1992",
language = "English",
volume = "105",
pages = "1--6",
journal = "Transactions of the Association of American Physicians",
issn = "0066-9458",

}

TY - JOUR

T1 - Endothelial cell heme oxygenase and ferritin induction by heme proteins

T2 - a possible mechanism limiting shock damage.

AU - Balla, J.

AU - Jacob, H. S.

AU - Balla, G.

AU - Nath, K.

AU - Vercellotti, G. M.

PY - 1992

Y1 - 1992

N2 - Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.

AB - Acutely, hemin sensitizes endothelial cells to oxidants but chronically protects the endothelium through the induction of ferritin. By releasing its heme, methemoglobin can sensitize endothelial cells in a fashion similar to free hemin. Furthermore, prolonged incubation with the endothelium allows methemoglobin to induce heme oxygenase and ferritin and concomitantly to modulate oxidant-mediated cytotoxicity. Methemoglobin but not hemoglobin, metmyoglobin or cytochrome c induces heme oxygenase and ferritin. Heme needs to be released from methemoglobin, since sodium cyanide, haptoglobin, and hemopexin inhibit the induction of these proteins. Neutrophils can oxidize hemoglobin to methemoglobin, which can subsequently induce both heme oxygenase and ferritin. We speculate that in shock with disseminated intravascular coagulation, marginated PMNs oxidize hemoglobin to heme-releasing methemoglobin. If critical defenses such as haptoglobin and hemopexin are overwhelmed, heme enters the endothelin cells, sensitizing them to oxidant damage. Endothelial cell adaptation via heme-induced heme oxygenase and ferritin production might limit ultimate progression to pulmonary and other vascular leak syndromes.

UR - http://www.scopus.com/inward/record.url?scp=0027033841&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027033841&partnerID=8YFLogxK

M3 - Article

VL - 105

SP - 1

EP - 6

JO - Transactions of the Association of American Physicians

JF - Transactions of the Association of American Physicians

SN - 0066-9458

ER -