EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells



Iron regulates hyperoxia-dependent human heme oxygenase 1 gene expression in pulmonary endothelial cells



American Journal of Respiratory Cell and Molecular Biology 20(4): 797-804



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.

(PDF emailed within 0-6 h: $19.90)

Accession: 010885321

Download citation: RISBibTeXText

PMID: 10101013

DOI: 10.1165/ajrcmb.20.4.3477



Related references

Induction of heme oxygenase 1 by hyperoxia is enhanced with iron in human pulmonary endothelial cells. Pediatric Research 41(4 PART 2): 307A, 1997

Ultrasound up-regulates expression of heme oxygenase-1 gene in endothelial cells. Journal of Medical Ultrasonics 42(4): 467-475, 2016

Regulatory role of heme oxygenase gene expression on heme dependent enzymes in endothelial cells using retroviral constructs. FASEB Journal 16(4): A174, March 20, 2002

Human heme oxygenase: cell cycle-dependent expression and DNA microarray identification of multiple gene responses after transduction of endothelial cells. Journal of Cellular Biochemistry 90(6): 1098-1111, 2003

Hyperoxia induction of human heme oxygenase 1 is a transcriptional response and is dependent upon free iron. Pediatric Research 43(4 PART 2): 336A, April, 1998

A cis-acting region regulates oxidized lipid-mediated induction of the human heme oxygenase-1 gene in endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology 23(8): 1416-1422, 2003

Insulin up-regulates heme oxygenase-1 expression in 3T3-L1 adipocytes via PI3-kinase- and PKC-dependent pathways and heme oxygenase-1-associated microRNA downregulation. Endocrinology 152(2): 384-393, 2011

Identification of an internal enhancer that regulates heme-mediated human heme oxygenase-1 gene expression. Journal of the American Society of Nephrology 14(Abstracts Issue): 274A-275A, November, 2003

Silymarin down-regulates HCV core and upregulates heme oxygenase-1 gene expression in the CNS3 replicon line of human liver cells. 2007

Retrovirus-mediated human heme oxygenase-1 (HO-1) gene transfer into rat endothelial cells: The effect of HO-1 inducers on the expression of cytokines. International Journal of Biochemistry and Cell Biology 35(3): 324-332, 2003

Retrovirus-mediated human heme oxygenase-1 gene transfer into human cells increases cellular protection against hyperoxia. Acta Haematologica (Basel) 103(Supplement 1): 74, July, 2000

Linoleyl hydroperoxide transcriptionally upregulates heme oxygenase-1 gene expression in human renal epithelial and aortic endothelial cells. Journal of the American Society of Nephrology 9(11): 1990-1997, 1998

Transfection of the human heme oxygenase gene into coronary endothelial cells protects against heme/hemoglobin toxicity. Journal of Investigative Medicine 43(SUPPL 2): 215A, 1995

Mitogen activated protein kinase regulates heme oxygenase-1 gene transcription after hyperoxia. Acta Haematologica (Basel) 103(Supplement 1): 60, July, 2000

Overexpression of heme oxygenase-1 in human pulmonary epithelial cells results in cell growth arrest and increased resistance to hyperoxia. Proceedings Of The National Academy Of Sciences Of The United States Of America. 93(19): 10393-10398, 1996