help button home button
AJRCMB
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fogg, S.
Right arrow Articles by Visner, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fogg, S.
Right arrow Articles by Visner, G. A.

Am. J. Respir. Cell Mol. Biol., Volume 20, Number 4, April, 1999 797-804

Iron Regulates Hyperoxia-Dependent Human Heme Oxygenase 1 Gene Expression in Pulmonary Endothelial Cells

Sandra Fogg, Anupam Agarwal, Harry S. Nick, and Gary A. Visner

Departments of Pediatrics, Medicine, and Neuroscience, University of Florida, Gainesville, Florida

The endothelium of the lung is sensitive to the toxic effects of oxygen, and early evidence of toxicity is characterized by protein leak and extravasation of red blood cells. The overproduction of oxygen free radicals plays a critical role in the pathophysiology of a hyperoxic lung injury. Recently, heme oxygenase 1 (HO-1), the rate-limiting enzyme in the metabolism of heme, has been found to have a protective role in oxidant injury. Our laboratory and others have identified HO-1 as a hyperoxia-inducible protein. In this study, we characterized HO-1 expression and evaluated its regulation in human pulmonary endothelial cells. Hyperoxia results in a relatively small increase in HO-1 expression; however, this induction is potentiated by heme and dramatically potentiated in the presence of free iron. This is probably more reflective of the in vivo situation in which there is extravasation of heme and iron products. We also found that HO-1 expression depended on chelatable iron. The iron chelator desferrioxamine not only inhibited the iron- dependent potentiation of HO-1 in response to hyperoxia but also inhibited both hyperoxia and basal expression. On the basis of inhibitor studies and nuclear run-on assays, we demonstrated that this induction is transcriptionally dependent. We also evaluated 4.5 kb of the human HO-1 promoter region and demonstrated that this region has promoter activity to the stimulus heme; however, there was no evidence of promoter activity to either iron or hyperoxia. This diversity of promoter activity to heme, heavy metals, and hyperoxia is unique to the human HO-1 gene.




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
S. W. Ryter, J. Alam, and A. M. K. Choi
Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications
Physiol Rev, April 1, 2006; 86(2): 583 - 650.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
L. Wu and R. Wang
Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications
Pharmacol. Rev., December 1, 2005; 57(4): 585 - 630.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
T. Morita
Heme Oxygenase and Atherosclerosis
Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1786 - 1795.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. J. Kornberg, L. C. Shaw, P. E. Spoerri, S. Caballero, and M. B. Grant
Focal Adhesion Kinase Overexpression Induces Enhanced Pathological Retinal Angiogenesis
Invest. Ophthalmol. Vis. Sci., December 1, 2004; 45(12): 4463 - 4469.
[Abstract] [Full Text] [PDF]

Home page
 J. Gerontol. A Biol. Sci. Med. Sci.Home page
H. F. Poon, V. Calabrese, G. Scapagnini, and D. A. Butterfield
Free Radicals: Key to Brain Aging and Heme Oxygenase as a Cellular Response to Oxidative Stress
J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2004; 59(5): M478 - M493.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
E. M. Sikorski, T. Hock, N. Hill-Kapturczak, and A. Agarwal
The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury
Am J Physiol Renal Physiol, March 1, 2004; 286(3): F425 - F441.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
A. Afzal, L.C. Shaw, S. Caballero, P.E. Spoerri, A.S. Lewin, D. Zeng, L. Belardinelli, and M.B. Grant
Reduction in Preretinal Neovascularization by Ribozymes That Cleave the A2B Adenosine Receptor mRNA
Circ. Res., September 19, 2003; 93(6): 500 - 506.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
L. C. Shaw, A. Afzal, A. S. Lewin, A. M. Timmers, P. E. Spoerri, and M. B. Grant
Decreased Expression of the Insulin-like Growth Factor 1 Receptor by Ribozyme Cleavage
Invest. Ophthalmol. Vis. Sci., September 1, 2003; 44(9): 4105 - 4113.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. Hill-Kapturczak, E. Sikorski, C. Voakes, J. Garcia, H. S. Nick, and A. Agarwal
An internal enhancer regulates heme- and cadmium-mediated induction of human heme oxygenase-1
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F515 - F523.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
P. Gong, A. I. Cederbaum, and N. Nieto
Increased Expression of Cytochrome P450 2E1 Induces Heme Oxygenase-1 through ERK MAPK Pathway
J. Biol. Chem., August 8, 2003; 278(32): 29693 - 29700.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
N. Hill-Kapturczak, C. Voakes, J. Garcia, G. Visner, H. S. Nick, and A. Agarwal
A cis-Acting Region Regulates Oxidized Lipid-Mediated Induction of the Human Heme Oxygenase-1 Gene in Endothelial Cells
Arterioscler. Thromb. Vasc. Biol., August 1, 2003; 23(8): 1416 - 1422.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Morse and A. M. K. Choi
Heme Oxygenase-1 . The "Emerging Molecule" Has Arrived
Am. J. Respir. Cell Mol. Biol., July 1, 2002; 27(1): 8 - 16.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
G. M. Balanos, K. L. Dorrington, and P. A. Robbins
Desferrioxamine elevates pulmonary vascular resistance in humans: potential for involvement of HIF-1
J Appl Physiol, June 1, 2002; 92(6): 2501 - 2507.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
N. Hill-Kapturczak, V. Thamilselvan, F. Liu, H. S. Nick, and A. Agarwal
Mechanism of heme oxygenase-1 gene induction by curcumin in human renal proximal tubule cells
Am J Physiol Renal Physiol, November 1, 2001; 281(5): F851 - F859.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. J. Lee, S. L. Camhi, B. Y. Chin, J. Alam, and A. M. K. Choi
AP-1 and STAT mediate hyperoxia-induced gene transcription of heme oxygenase-1
Am J Physiol Lung Cell Mol Physiol, July 1, 2000; 279(1): L175 - L182.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
A. AGARWAL and H. S. NICK
Renal Response to Tissue Injury: Lessons from Heme Oxygenase-1 GeneAblation and Expression
J. Am. Soc. Nephrol., May 1, 2000; 11(5): 965 - 973.
[Abstract] [Full Text]

Home page
 Exp. Biol. Med.Home page
R. Galbraith
Heme Oxygenase: Who Needs It?
Experimental Biology and Medicine, December 1, 1999; 222(3): 299 - 305.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
N. Hill-Kapturczak, L. Truong, V. Thamilselvan, G. A. Visner, H. S. Nick, and A. Agarwal
Smad7-dependent Regulation of Heme Oxygenase-1 by Transforming Growth Factor-beta in Human Renal Epithelial Cells
J. Biol. Chem., December 22, 2000; 275(52): 40904 - 40909.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Crit. Care Med.
Copyright © 1999 American Thoracic Society. 		  ATS Best of the Web