Published online before print January 31, 2002, doi: 10.1161/hh0402.105898
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2002 American Heart Association, Inc.
Molecular Medicine |
Sp1 Transcription Factor as a Molecular Target for Nitric Oxide– and Cyclic Nucleotide–Mediated Suppression of cGMP-Dependent Protein Kinase-I
Expression in Vascular Smooth Muscle Cells
From the Department of Molecular and Cellular Pathology (H.S., X.Y., X.C., T.C., T.L.), University of Alabama in Birmingham, Birmingham, Ala; and the Department of Medicine (G.A.S.), Division of Hematology and Oncology, Northwestern University Medical School, Chicago, Ill.
Correspondence to Thomas M. Lincoln, PhD, Dept of Pathology, University of Alabama in Birmingham, 1670 University Blvd, Volker Hall, Room G001, Birmingham, AL 35294-0019. E-mail lincoln{at}path.uab.edu
cGMP-dependent protein kinase (PKG) expression is highly variable and decreases in cultured vascular smooth muscle cells (VSMCs), exposure of cells to nitric oxide (NO), or in response to balloon catheter injury in vivo. In this study, the mechanisms of human type I PKG-
(PKG-I) gene expression were examined. Three structurally unrelated NO donors decreased PKG-I promoter activity after transfection of a promoter/luciferase construct in VSMCs. Promoter deletion analysis demonstrated that (1) a 120-bp promoter containing tandem Sp1 sites was sufficient to drive basal PKG-I promoter activity, and (2) NO was inhibitory at this site. Cyclic nucleotide analogues also suppressed PKG-I promoter activity with cAMP being more potent than cGMP. The effects of cyclic nucleotides to suppress PKG-I promoter activity were attenuated by a specific cAMP-dependent protein kinase (PKA) inhibitor. Single or double mutation of Sp1 binding sites abolished PKG-I expression. Moreover, Sp1 binding activity on the PKG-I promoter was detected in A7r5 cells, and this binding was inhibited by NO and cyclic nucleotides. These results indicate that PKG-I gene expression is driven by an Sp1 transcription mechanism, and that NO and cAMP inhibit Sp1-mediated PKG-I gene expression through separate mechanisms.
Key Words: cGMP • phosphorylation • gene regulation • inflammation • disease
This article has been cited by other articles:
 |
|
 |
|
  B. Cen, A. Deguchi, and I. B. Weinstein Activation of Protein Kinase G Increases the Expression of p21CIP1, p27KIP1, and Histidine Triad Protein 1 through Sp1 Cancer Res., July 1, 2008; 68(13): 5355 - 5362. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S. Elton and M. M. Martin Angiotensin II Type 1 Receptor Gene Regulation: Transcriptional and Posttranscriptional Mechanisms Hypertension, May 1, 2007; 49(5): 953 - 961. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Jiang and S. S Stojilkovic Molecular cloning and characterization of {alpha}1-soluble guanylyl cyclase gene promoter in rat pituitary cells J. Mol. Endocrinol., December 1, 2006; 37(3): 503 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zeng, S. Zhuang, J. Gloddek, C.-C. Tseng, G. R. Boss, and R. B. Pilz Regulation of cGMP-dependent Protein Kinase Expression by Rho and Kruppel-like Transcription Factor-4 J. Biol. Chem., June 23, 2006; 281(25): 16951 - 16961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Giordano, D. M. Magaletti, and E. A. Clark Nitric oxide and cGMP protein kinase (cGK) regulate dendritic-cell migration toward the lymph-node-directing chemokine CCL19 Blood, February 15, 2006; 107(4): 1537 - 1545. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sellak, C. Choi, N. Browner, and T. M. Lincoln Upstream Stimulatory Factors (USF-1/USF-2) Regulate Human cGMP-dependent Protein Kinase I Gene Expression in Vascular Smooth Muscle Cells J. Biol. Chem., May 6, 2005; 280(18): 18425 - 18433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Browner, H. Sellak, and T. M. Lincoln Downregulation of cGMP-dependent protein kinase expression by inflammatory cytokines in vascular smooth muscle cells Am J Physiol Cell Physiol, July 1, 2004; 287(1): C88 - C96. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Yao, L. Wang, D. Wei, W. Gong, M. Hassan, T.-T. Wu, P. Mansfield, J. Ajani, and K. Xie Association between Expression of Transcription Factor Sp1 and Increased Vascular Endothelial Growth Factor Expression, Advanced Stage, and Poor Survival in Patients with Resected Gastric Cancer Clin. Cancer Res., June 15, 2004; 10(12): 4109 - 4117. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H.-L. Xu, V. Gavrilyuk, H. M. Wolde, V. L. Baughman, and D. A. Pelligrino Regulation of rat pial arteriolar smooth muscle relaxation in vivo through multidrug resistance protein 5-mediated cGMP efflux Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H2020 - H2027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Gao, S. Dhanakoti, E. M. Trevino, X. Wang, F. C. Sander, A. D. Portugal, and J. U. Raj Role of cGMP-dependent protein kinase in development of tolerance to nitric oxide in pulmonary veins of newborn lambs Am J Physiol Lung Cell Mol Physiol, April 1, 2004; 286(4): L786 - L792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Wang, D. Wei, S. Huang, Z. Peng, X. Le, T. T. Wu, J. Yao, J. Ajani, and K. Xie Transcription Factor Sp1 Expression Is a Significant Predictor of Survival in Human Gastric Cancer Clin. Cancer Res., December 15, 2003; 9(17): 6371 - 6380. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Pilz and D. E. Casteel Regulation of Gene Expression by Cyclic GMP Circ. Res., November 28, 2003; 93(11): 1034 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Fan, E. Roy, L. Zhu, T. C. Murphy, M. Kozlowski, M. S. Nanes, and J. Rubin Nitric Oxide Donors Inhibit Luciferase Expression in a Promoter-independent Fashion J. Biol. Chem., March 14, 2003; 278(12): 10232 - 10238. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Horvath, A. Torbati, G. E. Conner, M. Salathe, and A. Wanner Systemic Ovalbumin Sensitization Downregulates Norepinephrine Uptake by Rabbit Aortic Smooth Muscle Cells Am. J. Respir. Cell Mol. Biol., December 1, 2002; 27(6): 746 - 751. [Abstract] [Full Text] [PDF]
|
|