|
|
Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-06-1693.
 Previous Article | Table of Contents | Next Article 
Blood, 1 February 2003, Vol. 101, No. 3, pp. 907-914
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Hypoxia-inducible factor-1 and hypoxia response elements mediate
the induction of plasminogen activator inhibitor-1 gene expression by
insulin in primary rat hepatocytes
Thomas Kietzmann,
Anatoly Samoylenko,
Ulrike Roth, and
Kurt Jungermann
From the Institut für Biochemie und Molekulare
Zellbiologie, Göttingen, Germany.
The expression of the plasminogen activator inhibitor-1
(PAI-1) gene is enhanced by insulin both in vivo
and in various cell types. Because insulin exerts a number of its
biologic activities via the phosphatidylinositol 3-kinase and protein
kinase B (PI3K/PKB) signaling pathway, it was the aim of the present
study to investigate the role of the PI3K/PKB pathway in the expression
of the PAI-1 gene and to identify the insulin responsive
promoter sequences. It was shown that the induction of PAI-1 mRNA and
protein expression by insulin and mild hypoxia could be repressed by
the PI3K inhibitor wortmannin. Overexpression of a constitutively
active PKB led to induction of PAI-1 mRNA expression and of luciferase
(Luc) activity from a gene construct containing 766 bp of the rat PAI-1 promoter. Mutation of the hypoxia response elements (HRE-1 and HRE-2)
in rat PAI-1 promoter, which could bind hypoxia inducible factor-1
(HIF-1), abolished the induction of PAI-1 by insulin and PKB.
Insulin and the constitutive active PKB also induced Luc expression in
cells transfected with the pGl3EPO-HRE Luc construct, containing 3 copies of the HRE from the erythropoietin gene in front of the SV40
promoter. Furthermore, insulin and the active PKB enhanced all 3 HIF
 -subunit protein levels and HIF-1 DNA-binding activity, as shown by
electrophoretic mobility shift assays (EMSAs). Thus, the
insulin-dependent activation of the PAI-1 gene expression can be mediated via the PI3K/PKB pathway and the transcription factor
HIF-1 binding to the HREs in the PAI-1 gene promoter.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. Chachami, A. Hatziefthimiou, P. Liakos, M. G. Ioannou, G. K. Koukoulis, S. Bonanou, P.-A. Molyvdas, G. Simos, and E. Paraskeva
Exposure of differentiated airway smooth muscle cells to serum stimulates both induction of hypoxia-inducible factor-1{alpha} and airway responsiveness to ACh
Am J Physiol Lung Cell Mol Physiol,
October 1, 2007;
293(4):
L913 - L922.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Flugel, A. Gorlach, C. Michiels, and T. Kietzmann
Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1{alpha} and Mediates Its Destabilization in a VHL-Independent Manner
Mol. Cell. Biol.,
May 1, 2007;
27(9):
3253 - 3265.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Liao, M. C. Hyman, D. A. Lawrence, and D. J. Pinsky
Molecular regulation of the PAI-1 gene by hypoxia: contributions of Egr-1, HIF-1{alpha}, and C/EBP{alpha}
FASEB J,
March 1, 2007;
21(3):
935 - 949.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Wang, S. S. Li, R. Segersvard, L. Strommer, K.-G. Sundqvist, J. Holgersson, and J. Permert
Hypoxia Inducible Factor-1 Mediates Effects of Insulin on Pancreatic Cancer Cells and Disturbs Host Energy Homeostasis
Am. J. Pathol.,
February 1, 2007;
170(2):
469 - 477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dekanty, S. Lavista-Llanos, M. Irisarri, S. Oldham, and P. Wappner
The insulin-PI3K/TOR pathway induces a HIF-dependent transcriptional response in Drosophila by promoting nuclear localization of HIF-{alpha}/Sima
J. Cell Sci.,
December 1, 2005;
118(23):
5431 - 5441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Zhou, S. Lechpammer, J. S. Greenberger, and J. Glowacki
Hypoxia Inhibition of Adipocytogenesis in Human Bone Marrow Stromal Cells Requires Transforming Growth Factor-{beta}/Smad3 Signaling
J. Biol. Chem.,
June 17, 2005;
280(24):
22688 - 22696.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kaur, F. W. Khwaja, E. A. Severson, S. L. Matheny, D. J. Brat, and E. G. Van Meir
Hypoxia and the hypoxia-inducible-factor pathway in glioma growth and angiogenesis
Neuro-oncol,
April 1, 2005;
7(2):
134 - 153.
[Abstract]
[PDF]
|
|
|
|
|
|
|
Q. Liu, U. Moller, D. Flugel, and T. Kietzmann
Induction of plasminogen activator inhibitor I gene expression by intracellular calcium via hypoxia-inducible factor-1
Blood,
December 15, 2004;
104(13):
3993 - 4001.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Galli, E Ceni, D W Crabb, T Mello, R Salzano, C Grappone, S Milani, E Surrenti, C Surrenti, and A Casini
Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPAR{gamma} independent mechanisms
Gut,
November 1, 2004;
53(11):
1688 - 1697.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Chachami, G. Simos, A. Hatziefthimiou, S. Bonanou, P.-A. Molyvdas, and E. Paraskeva
Cobalt Induces Hypoxia-Inducible Factor-1{alpha} Expression in Airway Smooth Muscle Cells by a Reactive Oxygen Species- and PI3K-Dependent Mechanism
Am. J. Respir. Cell Mol. Biol.,
November 1, 2004;
31(5):
544 - 551.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Sato, T. Tanaka, K. Maemura, T. Uchiyama, H. Sato, T. Maeno, T. Suga, T. Iso, Y. Ohyama, M. Arai, et al.
The PAI-1 Gene as a Direct Target of Endothelial PAS Domain Protein-1 in Adenocarcinoma A549 Cells
Am. J. Respir. Cell Mol. Biol.,
August 1, 2004;
31(2):
209 - 215.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Alam, E. T. Maizels, Y. Park, S. Ghaey, Z. J. Feiger, N. S. Chandel, and M. Hunzicker-Dunn
Follicle-stimulating Hormone Activation of Hypoxia-inducible Factor-1 by the Phosphatidylinositol 3-Kinase/AKT/Ras Homolog Enriched in Brain (Rheb)/Mammalian Target of Rapamycin (mTOR) Pathway Is Necessary for Induction of Select Protein Markers of Follicular Differentiation
J. Biol. Chem.,
May 7, 2004;
279(19):
19431 - 19440.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. C. Blouin, E. L. Page, G. M. Soucy, and D. E. Richard
Hypoxic gene activation by lipopolysaccharide in macrophages: implication of hypoxia-inducible factor 1{alpha}
Blood,
February 1, 2004;
103(3):
1124 - 1130.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Roth, K. Curth, T. G. Unterman, and T. Kietzmann
The Transcription Factors HIF-1 and HNF-4 and the Coactivator p300 Are Involved in Insulin-regulated Glucokinase Gene Expression via the Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway
J. Biol. Chem.,
January 23, 2004;
279(4):
2623 - 2631.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
