| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLE |
Department of Pharmacy, Center of Drug Research, University of Munich, 81377 Munich, Germany
Address all correspondence and requests for reprints to: Alexandra K. Kiemer, Ph.D., Department of Pharmacy, Center of Drug Research, Butenandtstrasse 5-13, 81377 Munich, Germany. E-mail: Alexandra. Kiemer{at}cup.uni-muenchen.de.
Background: Atrial natriuretic peptide (ANP) is a cardiovascular hormone possessing antiinflammatory and cytoprotective potential. The aim of this study was to characterize induction of heme oxygenase (HO)-1 by ANP in human umbilical vein endothelial cells (HUVEC). Methods: HUVEC were treated with ANP, 8-bromo-cyclic GMP (cGMP), or cANF in the presence or absence of various inhibitors. HO-1 was determined by Western blot and RT-PCR, c-jun N-terminal kinase (JNK) and ERK by the use of phospho-specific antibodies. Activator protein (AP)-1 activation was assessed by gelshift assay. Reporter gene assays were performed using native or mutated AP-1 binding sites of the HO-1 promoter. TNF-
-induced cell death was investigated by Hoechst staining, fluorescence-activated cell sorting analysis, caspase-3-measurement, and 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide test. Results: ANP (10-9–10-6 mol/liter) induced the expression of HO-1 protein and mRNA. Induction was mediated via the guanylate-cyclase-coupled receptor because 8-Br-cGMP mimicked the effect of ANP, whereas the clearance receptor agonist cANF did not induce HO-1. Endogenously produced cGMP also induced HO-1 because phosphodiesterase inhibition markedly elevated HO-1. The lack of effect of the cGMP-dependent protein kinase inhibitor 8-(4-chlorophenylthio)guanosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-pCT-cGMPS) suggested no involvement for this cGMP effector pathway in the signal transduction. ANP lead to activation of the transcription factor AP-1, and subsequently of JNK, as well as of ERK. Cotreatment of the cells with U0126 or SP600125, as well as reporter gene assays revealed the involvement of AP-1/JNK activation in HO-1 induction. Abrogation of HO-1 induction by PD-98059 showed also a role for ERK. Treatment of HUVEC with ANP did not protect from TNF--induced apoptosis. Conclusion: This work characterizes the induction of HO-1 by ANP in HUVEC, which is shown to be mediated via JNK/AP-1 and ERK pathways. ANP-induced HO-1 does not confer protection against TNF--induced apoptosis.
This article has been cited by other articles:
 |
|
 |
|
  T. O. Khor, M.-T. Huang, A. Prawan, Y. Liu, X. Hao, S. Yu, W. K. L. Cheung, J. Y. Chan, B. S. Reddy, C. S. Yang, et al. Increased Susceptibility of Nrf2 Knockout Mice to Colitis-Associated Colorectal Cancer Cancer Prevention Research, August 1, 2008; 1(3): 187 - 191. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Stone, G. L. Kolling, M. H. Lindner, and T. G. Obrig p38 Mitogen-Activated Protein Kinase Mediates Lipopolysaccharide and Tumor Necrosis Factor Alpha Induction of Shiga Toxin 2 Sensitivity in Human Umbilical Vein Endothelial Cells Infect. Immun., March 1, 2008; 76(3): 1115 - 1121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Martin, T. Tanos, A. B. Garcia, D. Martin, J. S. Gutkind, O. A. Coso, and M. J. Marinissen The G{alpha}12/13 Family of Heterotrimeric G Proteins and the Small GTPase RhoA Link the Kaposi Sarcoma-associated Herpes Virus G Protein-coupled Receptor to Heme Oxygenase-1 Expression and Tumorigenesis J. Biol. Chem., November 23, 2007; 282(47): 34510 - 34524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Gutterman Combating Nitrate Tolerance: A Novel Endogenous Mechanism Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1673 - 1676. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Alam and J. L. Cook How Many Transcription Factors Does It Take to Turn On the Heme Oxygenase-1 Gene? Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 166 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aburaya, K.-I. Tanaka, T. Hoshino, S. Tsutsumi, K. Suzuki, M. Makise, R. Akagi, and T. Mizushima Heme Oxygenase-1 Protects Gastric Mucosal Cells against Non-steroidal Anti-inflammatory Drugs J. Biol. Chem., November 3, 2006; 281(44): 33422 - 33432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Furst, S. B. Blumenthal, A. K. Kiemer, S. Zahler, and A. M. Vollmar Nuclear Factor-{kappa}B-Independent Anti-Inflammatory Action of Salicylate in Human Endothelial Cells: Induction of Heme Oxygenase-1 by the c-Jun N-Terminal Kinase/Activator Protein-1 Pathway J. Pharmacol. Exp. Ther., July 1, 2006; 318(1): 389 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Marinissen, T. Tanos, M. Bolos, M. R. de Sagarra, O. A. Coso, and A. Cuadrado Inhibition of Heme Oxygenase-1 Interferes with the Transforming Activity of the Kaposi Sarcoma Herpesvirusencoded G Protein-coupled Receptor J. Biol. Chem., April 21, 2006; 281(16): 11332 - 11346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H J Novaira, D S Ornellas, T M Ortiga-Carvalho, X M Zhang, J Souza-Menezes, S E Guggino, W B Guggino, and M M Morales Atrial natriuretic peptide modulates cystic fibrosis transmembrane conductance regulator chloride channel expression in rat proximal colon and human intestinal epithelial cells. J. Endocrinol., April 1, 2006; 189(1): 155 - 165. [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]
|
|
|
|
 |
|
 R. Furst, C. Brueckl, W. M. Kuebler, S. Zahler, F. Krotz, A. Gorlach, A. M. Vollmar, and A. K. Kiemer Atrial Natriuretic Peptide Induces Mitogen-Activated Protein Kinase Phosphatase-1 in Human Endothelial Cells via Rac1 and NAD(P)H Oxidase/Nox2-Activation Circ. Res., January 7, 2005; 96(1): 43 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Martin, A. I. Rojo, M. Salinas, R. Diaz, G. Gallardo, J. Alam, C. M. R. de Galarreta, and A. Cuadrado Regulation of Heme Oxygenase-1 Expression through the Phosphatidylinositol 3-Kinase/Akt Pathway and the Nrf2 Transcription Factor in Response to the Antioxidant Phytochemical Carnosol J. Biol. Chem., March 5, 2004; 279(10): 8919 - 8929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Kapoun, F. Liang, G. O'Young, D. L. Damm, D. Quon, R. T. White, K. Munson, A. Lam, G. F. Schreiner, and A. A. Protter B-Type Natriuretic Peptide Exerts Broad Functional Opposition to Transforming Growth Factor-{beta} in Primary Human Cardiac Fibroblasts: Fibrosis, Myofibroblast Conversion, Proliferation, and Inflammation Circ. Res., March 5, 2004; 94(4): 453 - 461. [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]
|
|
|
|
 |
|
 N. C. Weber, S. B. Blumenthal, T. Hartung, A. M. Vollmar, and A. K. Kiemer ANP inhibits TNF-{alpha}-induced endothelial MCP-1 expression--involvement of p38 MAPK and MKP-1 J. Leukoc. Biol., November 1, 2003; 74(5): 932 - 941. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rafiee, Y. Shi, K. A. Pritchard Jr., H. Ogawa, A. L. W. Eis, R. A. Komorowski, C. M. Fitzpatrick, J. S. Tweddell, S. B. Litwin, K. Mussatto, et al. Cellular Redistribution of Inducible Hsp70 Protein in the Human and Rabbit Heart in Response to the Stress of Chronic Hypoxia: ROLE OF PROTEIN KINASES J. Biol. Chem., October 31, 2003; 278(44): 43636 - 43644. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
