AJP - Lung Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Lung Cell Mol Physiol 281: L607-L615, 2001;
1040-0605/01 $5.00
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
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (21)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Andrew, A. S.
Right arrow Articles by Barchowsky, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Andrew, A. S.
Right arrow Articles by Barchowsky, A.
Vol. 281, Issue 3, L607-L615, September 2001

Nickel requires hypoxia-inducible factor-1alpha , not redox signaling, to induce plasminogen activator inhibitor-1

Angeline S. Andrew, Linda R. Klei, and Aaron Barchowsky

Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755

Human epidemiological and animal studies have associated inhalation of nickel dusts with an increased incidence of pulmonary fibrosis. At the cellular level, particulate nickel subsulfide inhibits fibrinolysis by transcriptionally inducing expression of plasminogen activator inhibitor (PAI)-1, an inhibitor of the urokinase-type plasminogen activator. Because nickel is known to mimic hypoxia, the present study examined whether nickel transcriptionally activates PAI-1 through the hypoxia-inducible factor (HIF)-1alpha signaling pathway. The involvement of the NADPH oxidase complex, reactive oxygen species, and kinases in mediating nickel-induced HIF-1alpha signaling was also investigated. Addition of nickel to BEAS-2B human airway epithelial cells increased HIF-1alpha protein levels and elevated PAI-1 mRNA levels. Pretreatment of cells with the extracellular signal-regulated kinase inhibitor U-0126 partially blocked HIF-1alpha protein and PAI-1 mRNA levels induced by nickel, whereas antioxidants and NADPH oxidase inhibitors had no effect. Pretreating cells with antisense, but not sense, oligonucleotides to HIF-1alpha mRNA abolished nickel-stimulated increases in PAI-1 mRNA. These data indicate that signaling through extracellular signal-regulated kinase and HIF-1alpha is required for nickel-induced transcriptional activation of PAI-1.

reduced nicotinamide adenine dinucleotide phosphate oxidase; nickel subsulfide; pulmonary fibrosis; mitogen-activated protein kinase; airway epithelium


This article has been cited by other articles:


Home page
 Am. J. Respir. Crit. Care Med.Home page
S. C. Wesselkamper, L. M. Case, L. N. Henning, M. T. Borchers, J. W. Tichelaar, J. M. Mason, N. Dragin, M. Medvedovic, M. A. Sartor, C. R. Tomlinson, et al.
Gene Expression Changes during the Development of Acute Lung Injury Role of Transforming Growth Factor {beta}
Am. J. Respir. Crit. Care Med., December 1, 2005; 172(11): 1399 - 1411.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
C. D. Kamat, D. E. Green, S. Curilla, L. Warnke, J. W. Hamilton, S. Sturup, C. Clark, and M. A. Ihnat
Role of HIF Signaling on Tumorigenesis in Response to Chronic Low-Dose Arsenic Administration
Toxicol. Sci., August 1, 2005; 86(2): 248 - 257.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
F. Gao, A. Barchowsky, A. A. Nemec, and J. P. Fabisiak
Microbial Stimulation by Mycoplasma fermentans Synergistically Amplifies IL-6 Release by Human Lung Fibroblasts in Response to Residual Oil Fly Ash (ROFA) and Nickel
Toxicol. Sci., October 1, 2004; 81(2): 467 - 479.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
J. Li, G. Davidson, Y. Huang, B.-H. Jiang, X. Shi, M. Costa, and C. Huang
Nickel Compounds Act through Phosphatidylinositol-3-kinase/Akt-Dependent, p70S6k-Independent Pathway to Induce Hypoxia Inducible Factor Transactivation and Cap43 Expression in Mouse Epidermal Cl41 Cells
Cancer Res., January 1, 2004; 64(1): 94 - 101.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
K. Salnikow, T. Davidson, Q. Zhang, L. C. Chen, W. Su, and M. Costa
The Involvement of Hypoxia-inducible Transcription Factor-1-dependent Pathway in Nickel Carcinogenesis
Cancer Res., July 1, 2003; 63(13): 3524 - 3530.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Barchowsky, N. V. Soucy, K. A. O'Hara, J. Hwa, T. L. Noreault, and A. S. Andrew
A Novel Pathway for Nickel-induced Interleukin-8 Expression
J. Biol. Chem., June 28, 2002; 277(27): 24225 - 24231.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
T. Fink, A. Kazlauskas, L. Poellinger, P. Ebbesen, and V. Zachar
Identification of a tightly regulated hypoxia-response element in the promoter of human plasminogen activator inhibitor-1
Blood, March 15, 2002; 99(6): 2077 - 2083.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
A. S. Andrew, L. R. Klei, and A. Barchowsky
AP-1-dependent induction of plasminogen activator inhibitor-1 by nickel does not require reactive oxygen
Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L616 - L623.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online