on June 12, 2003
Published online before print June 12, 2003, doi: 10.1161/01.ATV.0000081656.76378.A7
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on May 5, 2003
Accepted on June 2, 2003
cis-Acting Region Regulates Oxidized Lipid-Mediated Induction of the Human Heme Oxygenase-1 Gene in Endothelial Cells
Nathalie Hill-Kapturczak ;
From the Department of Medicine, Division of Nephrology, Hypertension and Transplantation (N.H.-K., C.V., J.G., A.A.), Department of Pediatrics (G.V.), Department of Neuroscience (H.S.N.), and Department of Biochemistry and Molecular Biology (H.S.N., A.A.), University of Florida, Gainesville, Fla.
* To whom correspondence should be addressed. E-mail: agarwal{at}nersp.nerdc.ufl.edu.
Objective--Several proatherogenic agents including oxidized LDL and its major component, 13-hydroxyperoxyoctadecadienoic acid (13-HPODE), upregulate heme oxygenase-1 (HO-1). Our previous studies have demonstrated that 13-HPODE-mediated HO-1 induction occurs via transcriptional mechanisms. The purpose of this study was to evaluate the molecular regulation and identify the signaling pathways involved in 13-HPODE-mediated HO-1 induction in human aortic endothelial cells.
Methods and Results--The half-life of HO-1 mRNA after stimulation with 13-HPODE was determined to be 
1.8 hours, and the induction of HO-1 was not dependent on increased mRNA stability. Antioxidants such as N-acetylcysteine, iron chelation with deferoxamine mesylate, and protein kinase C inhibition with Gö6976 blocked HO-1 induction. Using promoter constructs up to 9.1 kb, no significant reporter activity was observed in response to 13-HPODE. A 13-HPODE-inducible DNase I hypersensitive site was identified that maps to a region 10 to 11 kb from the transcription start site of the human HO-1 gene.
Conclusions--Based on the DNase I analysis, a -11.6-kb human HO-1 promoter construct was generated and elicited a 2.5-fold increase in reporter activity, indicating that 13-HPODE-mediated human HO-1 induction requires, at least in part, sequences that reside between 9.1 and 11.6 kb of the human HO-1 promoter.
Key words: atherosclerosis • heme oxygenase-1 • gene transcription • chromatin structure • oxidized LDL
This article has been cited by other articles:
 |
|
 |
|
  Q. Li, Y. Guo, Q. Ou, C. Cui, W.-J. Wu, W. Tan, X. Zhu, L. B. Lanceta, S. K. Sanganalmath, B. Dawn, et al. Gene Transfer of Inducible Nitric Oxide Synthase Affords Cardioprotection by Upregulating Heme Oxygenase-1 Via a Nuclear Factor-{kappa}B-Dependent Pathway Circulation, September 29, 2009; 120(13): 1222 - 1230. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Traylor, T. Hock, and N. Hill-Kapturczak Specificity protein 1 and Smad-dependent regulation of human heme oxygenase-1 gene by transforming growth factor-beta1 in renal epithelial cells Am J Physiol Renal Physiol, September 1, 2007; 293(3): F885 - F894. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Sikorski, T. Uo, R. S. Morrison, and A. Agarwal Pescadillo Interacts with the Cadmium Response Element of the Human Heme Oxygenase-1 Promoter in Renal Epithelial Cells J. Biol. Chem., August 25, 2006; 281(34): 24423 - 24430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. W. Ryter, J. Alam, and A. M. K. Choi Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic Applications Physiol Rev, April 1, 2006; 86(2): 583 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Wright, F. J. Schopfer, P. R. S. Baker, V. Vidyasagar, P. Powell, P. Chumley, K. E. Iles, B. A. Freeman, and A. Agarwal Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression. PNAS, March 14, 2006; 103(11): 4299 - 4304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Ameriso, A. R. Villamil, C. Zedda, J. C. Parodi, S. Garrido, M. I. Sarchi, M. Schultz, J. Boczkowski, and G. E. Sevlever Heme Oxygenase-1 Is Expressed in Carotid Atherosclerotic Plaques Infected by Helicobacter pylori and Is More Prevalent in Asymptomatic Subjects Stroke, September 1, 2005; 36(9): 1896 - 1900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Zmijewski, D. R. Moellering, C. L. Goffe, A. Landar, A. Ramachandran, and V. M. Darley-Usmar Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H852 - H861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Liby, T. Hock, M. M. Yore, N. Suh, A. E. Place, R. Risingsong, C. R. Williams, D. B. Royce, T. Honda, Y. Honda, et al. The Synthetic Triterpenoids, CDDO and CDDO-Imidazolide, Are Potent Inducers of Heme Oxygenase-1 and Nrf2/ARE Signaling Cancer Res., June 1, 2005; 65(11): 4789 - 4798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Sikorski, T. Hock, N. Hill-Kapturczak, and A. Agarwal The story so far: molecular regulation of the heme oxygenase-1 gene in renal injury Am J Physiol Renal Physiol, March 1, 2004; 286(3): F425 - F441. [Abstract] [Full Text] [PDF]
|
|