Circulation Research. 2001
Published online before print June 21, 2001, doi: 10.1161/hh1301.092678
Published online before print June 21, 2001, doi: 10.1161/hh1301.092678
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2001 American Heart Association, Inc.
Article |
Thrombin Activates the Hypoxia-Inducible Factor-1 Signaling Pathway in Vascular Smooth Muscle Cells
Role of the p22phox-Containing NADPH Oxidase
From the Institut für Kardiovaskuläre Physiologie (A.G., I.D., V.B.S.-K., R.P.B., R.B.), Klinikum der J.W. Goethe-Universität, Frankfurt/M.; Max-Planck-Institut für Molekulare Physiologie (U.B.-P.), Dortmund; and Institut für Biochemie und Molekulare Zellbiologie (U.R., T.K.), Universität Göttingen, Germany
Correspondence to Agnes Görlach, MD, Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, 60590 Frankfurt/M, Germany. E-mail A.Goerlach{at}em.uni-frankfurt.de
Abstract
Abstract—The
heterodimeric transcription factor hypoxia-inducible factor-1
(HIF-1) is activated under hypoxic conditions, resulting in the
upregulation of its target genes plasminogen
activator inhibitor-1 (PAI-1) and vascular
endothelial growth factor (VEGF). PAI-1 and VEGF are
also induced in response to vascular injury, which is characterized by
the activation of platelets and the coagulation cascade as well as
the generation of reactive oxygen species (ROS). However, it is not
known whether HIF-1 is also stimulated by thrombotic factors. We
investigated the role of thrombin, platelet-associated growth
factors, and ROS derived from the
p22phox-containing
NADPH oxidase in the activation of HIF-1 and the induction of its
target genes PAI-1 and VEGF in human vascular smooth muscle cells
(VSMCs). Thrombin, platelet-derived growth factor-AB (PDGF-AB), and
transforming growth factor-ß1
(TGF-ß1) upregulated HIF-1
protein in
cultured and native VSMCs. This response was accompanied by nuclear
accumulation of HIF-1 as well as by increased HIF-1 DNA-binding and
reporter gene activity. The thrombin-induced expression of HIF-1,
PAI-1, and VEGF was attenuated by antioxidant treatment as well as by
transfection of
p22phox
antisense oligonucleotides. Inhibition of p38
mitogen-activated protein kinase and
phosphatidylinositol-3-kinase significantly decreased thrombin-induced
HIF-1, PAI-1, and VEGF expression. These findings demonstrate that
the HIF-1 signaling pathway can be stimulated by thrombin and
platelet-associated growth factors and that a redox-sensitive cascade
activated by ROS derived from the
p22phox-containing
NADPH oxidase is crucially involved in this response.
Key Words: oxygen radicals • p22phox • platelets • vascular endothelial growth factor • plasminogen activator inhibitor-1
This article has been cited by other articles:
 |
|
 |
|
  G. Zhou, L. A. Dada, M. Wu, A. Kelly, H. Trejo, Q. Zhou, J. Varga, and J. I. Sznajder Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1 Am J Physiol Lung Cell Mol Physiol, December 1, 2009; 297(6): L1120 - L1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.G. Pringle, K.L. Kind, A.N. Sferruzzi-Perri, J.G. Thompson, and C.T. Roberts Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy Hum. Reprod. Update, November 19, 2009; (2009) dmp046v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Borissoff, H. M.H. Spronk, S. Heeneman, and H. ten Cate Is thrombin a key player in the 'coagulation-atherogenesis' maze? Cardiovasc Res, June 1, 2009; 82(3): 392 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Walter, N. Etienne-Selloum, D. Brasse, R. Schleiffer, V. Bekaert, P. M. Vanhoutte, A. Beretz, and V. B. Schini-Kerth Red Wine Polyphenols Prevent Acceleration of Neovascularization by Angiotensin II in the Ischemic Rat Hindlimb J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 699 - 707. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Milovanova, V. M. Bhopale, E. M. Sorokina, J. S. Moore, T. K. Hunt, M. Hauer-Jensen, O. C. Velazquez, and S. R. Thom Hyperbaric oxygen stimulates vasculogenic stem cell growth and differentiation in vivo J Appl Physiol, February 1, 2009; 106(2): 711 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2008; 13(4): 279 - 297. [Abstract] [PDF]
|
|
|
|
 |
|
 S. Lamy, V. Bedard, D. Labbe, H. Sartelet, C. Barthomeuf, D. Gingras, and R. Beliveau The Dietary Flavones Apigenin and Luteolin Impair Smooth Muscle Cell Migration and VEGF Expression through Inhibition of PDGFR-{beta} Phosphorylation Cancer Prevention Research, November 1, 2008; 1(6): 452 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Schober Chemokines in Vascular Dysfunction and Remodeling Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1950 - 1959. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Berchner-Pfannschmidt, S. Frede, C. Wotzlaw, and J. Fandrey Imaging of the hypoxia-inducible factor pathway: insights into oxygen sensing Eur. Respir. J., July 1, 2008; 32(1): 210 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. P. Deudero, C. Caramelo, M. C. Castellanos, F. Neria, R. Fernandez-Sanchez, O. Calabia, S. Penate, and F. R. Gonzalez-Pacheco Induction of Hypoxia-inducible Factor 1{alpha} Gene Expression by Vascular Endothelial Growth Factor J. Biol. Chem., April 25, 2008; 283(17): 11435 - 11444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-N. Jung, W. K. Yang, J. Kim, H. S. Kim, E. J. Kim, H. Yun, H. Park, S. S. Kim, W. Choe, I. Kang, et al. Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells Carcinogenesis, April 1, 2008; 29(4): 713 - 721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Kinney, U. M. Chandrasekharan, L. Mavrakis, and P. E. DiCorleto VEGF and thrombin induce MKP-1 through distinct signaling pathways: role for MKP-1 in endothelial cell migration Am J Physiol Cell Physiol, January 1, 2008; 294(1): C241 - C250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Page, D. A. Chan, A. J. Giaccia, M. Levine, and D. E. Richard Hypoxia-inducible Factor-1{alpha} Stabilization in Nonhypoxic Conditions: Role of Oxidation and Intracellular Ascorbate Depletion Mol. Biol. Cell, January 1, 2008; 19(1): 86 - 94. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Karshovska, A. Zernecke, G. Sevilmis, A. Millet, M. Hristov, C. D. Cohen, H. Schmid, F. Krotz, H.-Y. Sohn, V. Klauss, et al. Expression of HIF-1{alpha} in Injured Arteries Controls SDF-1{alpha} Mediated Neointima Formation in Apolipoprotein E Deficient Mice Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2540 - 2547. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. S. BelAiba, S. Bonello, C. Zahringer, S. Schmidt, J. Hess, T. Kietzmann, and A. Gorlach Hypoxia Up-Regulates Hypoxia-Inducible Factor-1{alpha} Transcription by Involving Phosphatidylinositol 3-Kinase and Nuclear Factor {kappa}B in Pulmonary Artery Smooth Muscle Cells Mol. Biol. Cell, December 1, 2007; 18(12): 4691 - 4697. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Baron-Menguy, A. Bocquet, A.-L. Guihot, D. Chappard, M.-J. Amiot, R. Andriantsitohaina, L. Loufrani, and D. Henrion Effects of red wine polyphenols on postischemic neovascularization model in rats: low doses are proangiogenic, high doses anti-angiogenic FASEB J, November 1, 2007; 21(13): 3511 - 3521. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 M.-C. Lauzier, E. L. Page, M. D. Michaud, and D. E. Richard Differential Regulation of Hypoxia-Inducible Factor-1 through Receptor Tyrosine Kinase Transactivation in Vascular Smooth Muscle Cells Endocrinology, August 1, 2007; 148(8): 4023 - 4031. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Brune and J. Zhou Nitric oxide and superoxide: Interference with hypoxic signaling Cardiovasc Res, July 15, 2007; 75(2): 275 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Doyle and N. Caplice Plaque Neovascularization and Antiangiogenic Therapy for Atherosclerosis J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2073 - 2080. [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]
|
|
|
|
|
|
A. A. Kazi and R. D. Koos Estrogen-Induced Activation of Hypoxia-Inducible Factor-1{alpha}, Vascular Endothelial Growth Factor Expression, and Edema in the Uterus Are Mediated by the Phosphatidylinositol 3-Kinase/Akt Pathway Endocrinology, May 1, 2007; 148(5): 2363 - 2374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bonello, C. Zahringer, R. S. BelAiba, T. Djordjevic, J. Hess, C. Michiels, T. Kietzmann, and A. Gorlach Reactive Oxygen Species Activate the HIF-1{alpha} Promoter Via a Functional NF{kappa}B Site Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-X. Chen, H. Zeng, Q.-H. Tuo, H. Yu, B. Meyrick, and J. L. Aschner NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after hypoxia-reoxygenation Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1664 - H1674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, A. E. Damdimopoulos, G. Spyrou, and B. Brune Thioredoxin 1 and Thioredoxin 2 Have Opposed Regulatory Functions on Hypoxia-inducible Factor-1{alpha} J. Biol. Chem., March 9, 2007; 282(10): 7482 - 7490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ramanathan, G. Pinhal-Enfield, I. Hao, and S. J. Leibovich Synergistic Up-Regulation of Vascular Endothelial Growth Factor (VEGF) Expression in Macrophages by Adenosine A2A Receptor Agonists and Endotoxin Involves Transcriptional Regulation via the Hypoxia Response Element in the VEGF Promoter Mol. Biol. Cell, January 1, 2007; 18(1): 14 - 23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Lee, S. Y. Park, E. K. Lee, C. G. Park, H. C. Chung, S. Y. Rha, Y. K. Kim, G.-U. Bae, B. K. Kim, J.-W. Han, et al. Activation of Hypoxia-Inducible Factor-1{alpha} Is Necessary for Lysophosphatidic Acid-Induced Vascular Endothelial Growth Factor Expression. Clin. Cancer Res., November 1, 2006; 12(21): 6351 - 6358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ke and M. Costa Hypoxia-Inducible Factor-1 (HIF-1) Mol. Pharmacol., November 1, 2006; 70(5): 1469 - 1480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-X. Chen, H. Zeng, M. L Lawrence, T. S. Blackwell, and B. Meyrick Angiopoietin-1-induced angiogenesis is modulated by endothelial NADPH oxidase Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1563 - H1572. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. McMahon, M. Charbonneau, S. Grandmont, D. E. Richard, and C. M. Dubois Transforming Growth Factor beta1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression J. Biol. Chem., August 25, 2006; 281(34): 24171 - 24181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-Y. Zhu, E. Daghini, A. R. Chade, M. Rodriguez-Porcel, C. Napoli, A. Lerman, and L. O. Lerman Role of Oxidative Stress in Remodeling of the Myocardial Microcirculation in Hypertension Arterioscler Thromb Vasc Biol, August 1, 2006; 26(8): 1746 - 1752. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Clempus and K. K. Griendling Reactive oxygen species signaling in vascular smooth muscle cells Cardiovasc Res, July 15, 2006; 71(2): 216 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. R. Moreno, K-R. Purushothaman, M. Sirol, A. P. Levy, and V. Fuster Neovascularization in Human Atherosclerosis Circulation, May 9, 2006; 113(18): 2245 - 2252. [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. BelAiba, T. Djordjevic, S. Bonello, F. Artunc, F. Lang, J. Hess, and A. Gorlach The Serum- and Glucocorticoid-Inducible Kinase Sgk-1 Is Involved in Pulmonary Vascular Remodeling: Role in Redox-Sensitive Regulation of Tissue Factor by Thrombin Circ. Res., March 31, 2006; 98(6): 828 - 836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Ateghang, M. Wartenberg, M. Gassmann, and H. Sauer Regulation of cardiotrophin-1 expression in mouse embryonic stem cells by HIF-1{alpha} and intracellular reactive oxygen species J. Cell Sci., March 15, 2006; 119(6): 1043 - 1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Q. Liu, I. N. Zelko, E. M. Erbynn, J. S. K. Sham, and R. J. Folz Hypoxic pulmonary hypertension: role of superoxide and NADPH oxidase (gp91phox) Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L2 - L10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Wenger, D. P. Stiehl, and G. Camenisch Integration of Oxygen Signaling at the Consensus HRE Sci. Signal., October 18, 2005; 2005(306): re12 - re12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Kazi, J. M. Jones, and R. D. Koos Chromatin Immunoprecipitation Analysis of Gene Expression in the Rat Uterus in Vivo: Estrogen-Induced Recruitment of Both Estrogen Receptor {alpha} and Hypoxia-Inducible Factor 1 to the Vascular Endothelial Growth Factor Promoter Mol. Endocrinol., August 1, 2005; 19(8): 2006 - 2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Al-Shabrawey, M. Bartoli, A. B. El-Remessy, D. H. Platt, S. Matragoon, M. A. Behzadian, R. W. Caldwell, and R. B. Caldwell Inhibition of NAD(P)H Oxidase Activity Blocks Vascular Endothelial Growth Factor Overexpression and Neovascularization during Ischemic Retinopathy Am. J. Pathol., August 1, 2005; 167(2): 599 - 607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. El Bedoui, M.-H. Oak, P. Anglard, and V. B. Schini-Kerth Catechins prevent vascular smooth muscle cell invasion by inhibiting MT1-MMP activity and MMP-2 expression Cardiovasc Res, August 1, 2005; 67(2): 317 - 325. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Gaber, R Dziurla, R Tripmacher, G R Burmester, and F Buttgereit Hypoxia inducible factor (HIF) in rheumatology: low O2! See what HIF can do! Ann Rheum Dis, July 1, 2005; 64(7): 971 - 980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Kairuz, M. N. Barber, C. R. Anderson, M. Kanagasundaram, G. R. Drummond, and R. L. Woods C-type natriuretic peptide (CNP) suppresses plasminogen activator inhibitor-1 (PAI-1) in vivo Cardiovasc Res, June 1, 2005; 66(3): 574 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Ziel, V. Grishko, C. C. Campbell, J. F. Breit, G. L. Wilson, and M. N. Gillespie Oxidants in signal transduction: impact on DNA integrity and gene expression FASEB J, March 1, 2005; 19(3): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Djordjevic, R. S. BelAiba, S. Bonello, J. Pfeilschifter, J. Hess, and A. Gorlach Human Urotensin II Is a Novel Activator of NADPH Oxidase in Human Pulmonary Artery Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2005; 25(3): 519 - 525. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H.M. Ellmark, G. J. Dusting, M. Ng Tang Fui, N. Guzzo-Pernell, and G. R. Drummond The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle Cardiovasc Res, February 1, 2005; 65(2): 495 - 504. [Abstract] [Full Text] [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]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
S. Forrest and C. McNamara Id Family of Transcription Factors and Vascular Lesion Formation Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2014 - 2020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Oak, J. El Bedoui, P. Anglard, and V. B. Schini-Kerth Red Wine Polyphenolic Compounds Strongly Inhibit Pro-Matrix Metalloproteinase-2 Expression and Its Activation in Response to Thrombin via Direct Inhibition of Membrane Type 1-Matrix Metalloproteinase in Vascular Smooth Muscle Cells Circulation, September 28, 2004; 110(13): 1861 - 1867. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hopfl, O. Ogunshola, and M. Gassmann HIFs and tumors--causes and consequences Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R608 - R623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Khatri, C. Johnson, R. Magid, S. M. Lessner, K. M. Laude, S. I. Dikalov, D. G. Harrison, H.-J. Sung, Y. Rong, and Z. S. Galis Vascular Oxidant Stress Enhances Progression and Angiogenesis of Experimental Atheroma Circulation, February 3, 2004; 109(4): 520 - 525. [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]
|
|
|
|
|
|
T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mottet, V. Dumont, Y. Deccache, C. Demazy, N. Ninane, M. Raes, and C. Michiels Regulation of Hypoxia-inducible Factor-1{alpha} Protein Level during Hypoxic Conditions by the Phosphatidylinositol 3-Kinase/Akt/Glycogen Synthase Kinase 3{beta} Pathway in HepG2 Cells J. Biol. Chem., August 15, 2003; 278(33): 31277 - 31285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kisliouk, N. Levy, A. Hurwitz, and R. Meidan Presence and Regulation of Endocrine Gland Vascular Endothelial Growth Factor/Prokineticin-1 and Its Receptors in Ovarian Cells J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3700 - 3707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. El-Remessy, M. A. Behzadian, G. Abou-Mohamed, T. Franklin, R. W. Caldwell, and R. B. Caldwell Experimental Diabetes Causes Breakdown of the Blood-Retina Barrier by a Mechanism Involving Tyrosine Nitration and Increases in Expression of Vascular Endothelial Growth Factor and Urokinase Plasminogen Activator Receptor Am. J. Pathol., June 1, 2003; 162(6): 1995 - 2004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Oak, M. Chataigneau, T. Keravis, T. Chataigneau, A. Beretz, R. Andriantsitohaina, J.-C. Stoclet, S.-J. Chang, and V. B. Schini-Kerth Red Wine Polyphenolic Compounds Inhibit Vascular Endothelial Growth Factor Expression in Vascular Smooth Muscle Cells by Preventing the Activation of the p38 Mitogen-Activated Protein Kinase Pathway Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1001 - 1007. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z.-Z. Yang, A. Y. Zhang, F.-X. Yi, P.-L. Li, and A.-P. Zou Redox regulation of HIF-1alpha levels and HO-1 expression in renal medullary interstitial cells Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1207 - F1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhou, T. Schmid, and B. Brune Tumor Necrosis Factor-{alpha} Causes Accumulation of a Ubiquitinated Form of Hypoxia Inducible Factor-1{alpha} through a Nuclear Factor-{kappa}B-Dependent Pathway Mol. Biol. Cell, June 1, 2003; 14(6): 2216 - 2225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. A. Duyndam, S. T. M. Hulscher, E. van der Wall, H. M. Pinedo, and E. Boven Evidence for a Role of p38 Kinase in Hypoxia-inducible Factor 1-independent Induction of Vascular Endothelial Growth Factor Expression by Sodium Arsenite J. Biol. Chem., February 21, 2003; 278(9): 6885 - 6895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Minami, Md. R. Abid, J. Zhang, G. King, T. Kodama, and W. C. Aird Thrombin Stimulation of Vascular Adhesion Molecule-1 in Endothelial Cells Is Mediated by Protein Kinase C (PKC)-delta -NF-kappa B and PKC-zeta -GATA Signaling Pathways J. Biol. Chem., February 21, 2003; 278(9): 6976 - 6984. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kietzmann, A. Samoylenko, U. Roth, and K. Jungermann Hypoxia-inducible factor-1 and hypoxia response elements mediate the induction of plasminogen activator inhibitor-1 gene expression by insulin in primary rat hepatocytes Blood, February 1, 2003; 101(3): 907 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Page, G. A. Robitaille, J. Pouyssegur, and D. E. Richard Induction of Hypoxia-inducible Factor-1alpha by Transcriptional and Translational Mechanisms J. Biol. Chem., December 6, 2002; 277(50): 48403 - 48409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Schroedl, D. S. McClintock, G. R. S. Budinger, and N. S. Chandel Hypoxic but not anoxic stabilization of HIF-1alpha requires mitochondrial reactive oxygen species Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L922 - L931. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Evans, I. D. Goldfine, B. A. Maddux, and G. M. Grodsky Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes Endocr. Rev., October 1, 2002; 23(5): 599 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Guo, A. P. Mazar, J.-J. Lebrun, and S. A. Rabbani An Antiangiogenic Urokinase-derived Peptide Combined with Tamoxifen Decreases Tumor Growth and Metastasis in a Syngeneic Model of Breast Cancer Cancer Res., August 15, 2002; 62(16): 4678 - 4684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kaluz, M. Kaluzova, A. Chrastina, P. L. Olive, S. Pastorekova, J. Pastorek, M. I. Lerman, and E. J. Stanbridge Lowered Oxygen Tension Induces Expression of the Hypoxia Marker MN/Carbonic Anhydrase IX in the Absence of Hypoxia-inducible Factor 1{alpha} Stabilization: A Role for Phosphatidylinositol 3'-Kinase Cancer Res., August 1, 2002; 62(15): 4469 - 4477. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. WENGER Cellular adaptation to hypoxia: O2-sensing protein hydroxylases, hypoxia-inducible transcription factors, and O2-regulated gene expression FASEB J, August 1, 2002; 16(10): 1151 - 1162. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
A. M. Arsham, D. R. Plas, C. B. Thompson, and M. C. Simon Phosphatidylinositol 3-Kinase/Akt Signaling Is Neither Required for Hypoxic Stabilization of HIF-1alpha nor Sufficient for HIF-1-dependent Target Gene Transcription J. Biol. Chem., April 19, 2002; 277(17): 15162 - 15170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alvarez-Tejado, A. Alfranca, J. Aragones, A. Vara, M. O. Landazuri, and L. del Peso Lack of Evidence for the Involvement of the Phosphoinositide 3-Kinase/Akt Pathway in the Activation of Hypoxia-inducible Factors by Low Oxygen Tension J. Biol. Chem., April 12, 2002; 277(16): 13508 - 13517. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. P. Souza, X. Liu, A. Samouilov, P. Kuppusamy, F. R. M. Laurindo, and J. L. Zweier Quantitation of superoxide generation and substrate utilization by vascular NAD(P)H oxidase Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H466 - H474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Sen, S. Khanna, M. Venojarvi, P. Trikha, E. C. Ellison, T. K. Hunt, and S. Roy Copper-induced vascular endothelial growth factor expression and wound healing Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1821 - H1827. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Herkert, I. Diebold, R. P. Brandes, J. Hess, R. Busse, and A. Gorlach NADPH Oxidase Mediates Tissue Factor-Dependent Surface Procoagulant Activity by Thrombin in Human Vascular Smooth Muscle Cells Circulation, April 30, 2002; 105(17): 2030 - 2036. [Abstract] [Full Text] [PDF]
|
|