|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 279, Issue 10, 8919-8929, March 5, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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*
||
From the
Instituto de Investigaciones Biomédicas and the Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain, the ¶Department of Biochemistry and Molecular Biology, Louisiana State University Health Science Center, New Orleans, Louisiana 70112, and the Departamento de Bioquímica, Facultad de Medicina, Universidad de las Palmas de Gran Canaria, 35016 Gran Canaria, Spain
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal against multiple apoptotic insults. In addition, phase II enzymes such as heme oxygenase-1 (HO-1) protect cells against diverse toxins and oxidative stress. In this work, we describe a link between these defense systems at the level of transcriptional regulation of the antioxidant enzyme HO-1. The herb-derived phenol carnosol induced HO-1 expression at both mRNA and protein levels. Luciferase reporter assays indicated that carnosol targeted the mouse ho1 promoter at two enhancer regions comprising the antioxidant response elements (AREs). Moreover, carnosol increased the nuclear levels of Nrf2, a transcription factor governing AREs. Electrophoretic mobility shift assays and luciferase reporter assays with a dominant-negative Nrf2 mutant indicated that carnosol increased the binding of Nrf2 to ARE and induced Nrf2-dependent activation of the ho1 promoter. While investigating the signaling pathways responsible for HO-1 induction, we observed that carnosol activated the ERK, p38, and JNK pathways as well as the survival pathway driven by PI3K. Inhibition of PI3K reduced the increase in Nrf2 protein levels and activation of the ho1 promoter. Expression of active PI3K-CAAX (where A is aliphatic amino acid) was sufficient to activate AREs. The use of dominant-negative mutants of protein kinase C
and Akt1, two kinases downstream from PI3K, demonstrated a requirement for active Akt1, but not protein kinase C. Moreover, the long-term antioxidant effect of carnosol was partially blocked by PI3K or HO-1 inhibitors, further demonstrating that carnosol attenuates oxidative stress through a pathway that involves PI3K and HO-1.
Received for publication, September 2, 2003 , and in revised form, December 4, 2003.
* This work was supported by Grant SAF2001-0545 from the Ministerio de Ciencia y Tecnología and Grant 08.5/0048/2001 from the Comunidad Autónoma de Madrid (to A. C.) and by Grants FEDER-97/0602 and PI-2002/168 from the Comunidad Autónoma de Canarias (to C. M. R. d. G.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
|| To whom correspondence should addressed: Dept. de Bioquímica, Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain. Tel.: 34-91-497-5327; Fax: 34-91-585-4401; E-mail: antonio.cuadrado{at}uam.es.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. A. Morales, D. Gutman, P. J. Cejas, K. P. Lee, and L. H. Boise Reactive Oxygen Species Are Not Required for an Arsenic Trioxide-induced Antioxidant Response or Apoptosis J. Biol. Chem., May 8, 2009; 284(19): 12886 - 12895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Burger, F. Xiang, L. Hammoud, X. Lu, and Q. Feng Role of heme oxygenase-1 in the cardioprotective effects of erythropoietin during myocardial ischemia and reperfusion Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H84 - H93. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Geraldes, K. Yagi, Y. Ohshiro, Z. He, Y. Maeno, J. Yamamoto-Hiraoka, C. Rask-Madsen, S. W. Chung, M. A. Perrella, and G. L. King Selective Regulation of Heme Oxygenase-1 Expression and Function by Insulin through IRS1/Phosphoinositide 3-Kinase/Akt-2 Pathway J. Biol. Chem., December 5, 2008; 283(49): 34327 - 34336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Calo and P. A. Davis EPO induces rise in serum ADMA but does not prevent the increase in NO release: the likely involvement of HO-1 Nephrol. Dial. Transplant., September 1, 2008; 23(9): 3035 - 3036. [Full Text] [PDF]
|
|
|
|
 |
|
 N. G. Innamorato, A. I. Rojo, A. J. Garcia-Yague, M. Yamamoto, M. L. de Ceballos, and A. Cuadrado The Transcription Factor Nrf2 Is a Therapeutic Target against Brain Inflammation J. Immunol., July 1, 2008; 181(1): 680 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Fledderus, R. A. Boon, O. L. Volger, H. Hurttila, S. Yla-Herttuala, H. Pannekoek, A.-L. Levonen, and A. J.G. Horrevoets KLF2 Primes the Antioxidant Transcription Factor Nrf2 for Activation in Endothelial Cells Arterioscler. Thromb. Vasc. Biol., July 1, 2008; 28(7): 1339 - 1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zhang and H. J. Forman Acrolein Induces Heme Oxygenase-1 through PKC-{delta} and PI3K in Human Bronchial Epithelial Cells Am. J. Respir. Cell Mol. Biol., April 1, 2008; 38(4): 483 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A Calo, P. A Davis, E. Pagnin, L. Bertipaglia, A. Naso, A. Piccoli, R. Corradini, M. Spinello, V. Savica, and L. D. Libera Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1: studies in humans and in an animal model Nephrol. Dial. Transplant., March 1, 2008; 23(3): 890 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Hsieh, C.-S. Rau, M.-W. Hsieh, Y.-C. Chen, S.-F. Jeng, T.-H. Lu, and S.-S. Chen Simvastatin-Induced Heme Oxygenase-1 Increases Apoptosis of Neuro 2A Cells in Response to Glucose Deprivation Toxicol. Sci., January 1, 2008; 101(1): 112 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Canas, T. Valero, M. Villarroya, E. Montell, J. Verges, A. G. Garcia, and M. G. Lopez Chondroitin Sulfate Protects SH-SY5Y Cells from Oxidative Stress by Inducing Heme Oxygenase-1 via Phosphatidylinositol 3-Kinase/Akt J. Pharmacol. Exp. Ther., December 1, 2007; 323(3): 946 - 953. [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]
|
|
|
|
 |
|
 J.-T. Hsu, W.-H. Kan, C.-H. Hsieh, M. A. Choudhry, M. G. Schwacha, K. I. Bland, and I. H. Chaudry Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation J. Leukoc. Biol., October 1, 2007; 82(4): 1019 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-H. Li, J.-H. Jang, H.-K. Na, Y.-N. Cha, and Y.-J. Surh Carbon Monoxide Produced by Heme Oxygenase-1 in Response to Nitrosative Stress Induces Expression of Glutamate-Cysteine Ligase in PC12 Cells via Activation of Phosphatidylinositol 3-Kinase and Nrf2 Signaling J. Biol. Chem., September 28, 2007; 282(39): 28577 - 28586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Dai, S. Vaughn, Y. Zhang, E. T. Wang, G. Garcia-Cardena, and M. A. Gimbrone Jr Biomechanical Forces in Atherosclerosis-Resistant Vascular Regions Regulate Endothelial Redox Balance via Phosphoinositol 3-Kinase/Akt-Dependent Activation of Nrf2 Circ. Res., September 28, 2007; 101(7): 723 - 733. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pugazhenthi, L. Akhov, G. Selvaraj, M. Wang, and J. Alam Regulation of heme oxygenase-1 expression by demethoxy curcuminoids through Nrf2 by a PI3-kinase/Akt-mediated pathway in mouse beta-cells Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E645 - E655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-m. Liu, M. A. Azam, K. J. Peyton, D. Ensenat, A. N. Keswani, H. Wang, and W. Durante Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries Cardiovasc Res, April 1, 2007; 74(1): 169 - 179. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rajesh, R. Sagar, S. Singh, R. Kumar, A. K. Sharma, J. Prasad, S. Singh, M. Gupta, R. K. Sharma, S. C. Puri, et al. Cytoprotective Effect of Podophyllum hexandrum Against Gamma Radiation is Mediated via Hemopoietic System Stimulation and Up-Regulation of Heme-oxygenase-1 and the Prosurvival Multidomain Protein Bcl-2 Integr Cancer Ther, March 1, 2007; 6(1): 54 - 65. [Abstract] [PDF]
|
|
|
|
|
|
K. R. Brunt, K. K. Fenrich, G. Kiani, M. Yat Tse, S. C. Pang, C. A. Ward, and L. G. Melo Protection of Human Vascular Smooth Muscle Cells From H2O2-Induced Apoptosis Through Functional Codependence Between HO-1 and AKT Arterioscler. Thromb. Vasc. Biol., September 1, 2006; 26(9): 2027 - 2034. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Salazar, A. I. Rojo, D. Velasco, R. M. de Sagarra, and A. Cuadrado Glycogen Synthase Kinase-3beta Inhibits the Xenobiotic and Antioxidant Cell Response by Direct Phosphorylation and Nuclear Exclusion of the Transcription Factor Nrf2 J. Biol. Chem., May 26, 2006; 281(21): 14841 - 14851. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 H. Abuarqoub, R. Foresti, C. J. Green, and R. Motterlini Heme oxygenase-1 mediates the anti-inflammatory actions of 2'-hydroxychalcone in RAW 264.7 murine macrophages Am J Physiol Cell Physiol, April 1, 2006; 290(4): C1092 - C1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. W. Leffler, H. Parfenova, J. H. Jaggar, and R. Wang Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation J Appl Physiol, March 1, 2006; 100(3): 1065 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Andreadi, L. M. Howells, P. A. Atherfold, and M. M. Manson Involvement of Nrf2, p38, B-Raf, and Nuclear Factor-{kappa}B, but Not Phosphatidylinositol 3-Kinase, in Induction of Hemeoxygenase-1 by Dietary Polyphenols Mol. Pharmacol., March 1, 2006; 69(3): 1033 - 1040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Davis, E. Pagnin, A. Semplicini, A. Avogaro, and L. A. Calo Insulin Signaling, Glucose Metabolism, and the Angiotensin II Signaling System: Studies in Bartter's/Gitelman's syndromes Diabetes Care, February 1, 2006; 29(2): 469 - 471. [Full Text] [PDF]
|
|
|
|
|
|
H. Zhang, H. Liu, K. E. Iles, R.-M. Liu, E. M. Postlethwait, Y. Laperche, and H. J. Forman 4-Hydroxynonenal Induces Rat {gamma}-Glutamyl Transpeptidase through Mitogen-Activated Protein Kinase-Mediated Electrophile Response Element/Nuclear Factor Erythroid 2-Related Factor 2 Signaling Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 174 - 181. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z.-H. Chen, Y. Saito, Y. Yoshida, A. Sekine, N. Noguchi, and E. Niki 4-Hydroxynonenal Induces Adaptive Response and Enhances PC12 Cell Tolerance Primarily through Induction of Thioredoxin Reductase 1 via Activation of Nrf2 J. Biol. Chem., December 23, 2005; 280(51): 41921 - 41927. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Rushworth, X.-L. Chen, N. Mackman, R. M. Ogborne, and M. A. O'Connell Lipopolysaccharide-Induced Heme Oxygenase-1 Expression in Human Monocytic Cells Is Mediated via Nrf2 and Protein Kinase C J. Immunol., October 1, 2005; 175(7): 4408 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Ogborne, S. A. Rushworth, and M. A. O'Connell {alpha}-Lipoic Acid-Induced Heme Oxygenase-1 Expression Is Mediated by Nuclear Factor Erythroid 2-Related Factor 2 and p38 Mitogen-Activated Protein Kinase in Human Monocytic Cells Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2100 - 2105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Calo, P. A. Davis, A. Semplicini, and A. C. Pessina L-Carnitine and erythropoiesis: relationship with haeme oxygenase-1 Nephrol. Dial. Transplant., August 1, 2005; 20(8): 1769 - 1770. [Full Text] [PDF]
|
|
|
|
|
|
R. Feng, Y. Lu, L. L. Bowman, Y. Qian, V. Castranova, and M. Ding Inhibition of Activator Protein-1, NF-{kappa}B, and MAPKs and Induction of Phase 2 Detoxifying Enzyme Activity by Chlorogenic Acid J. Biol. Chem., July 29, 2005; 280(30): 27888 - 27895. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wijayanti, T. Kietzmann, and S. Immenschuh Heme Oxygenase-1 Gene Activation by the NAD(P)H Oxidase Inhibitor 4-(2-Aminoethyl) Benzenesulfonyl Fluoride via a Protein Kinase B, p38-dependent Signaling Pathway in Monocytes J. Biol. Chem., June 10, 2005; 280(23): 21820 - 21829. [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]
|
|
|
|
|
|
L. A. Calo, E. Pagnin, P. A. Davis, M. Sartori, A. Semplicini, A. C. Pessina, S. Wolfrum, Y. Rikitake, J. K. Liao, A. Dendorfer, et al. Rho Kinase Inhibition and Vascular Protection: Support From Studies in Bartter and Gitelman Syndrome Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): e34 - e35. [Full Text] [PDF]
|
|
|
|
|
|
S. W. Chung, Y.-H. Chen, and M. A. Perrella Role of Ets-2 in the Regulation of Heme Oxygenase-1 by Endotoxin J. Biol. Chem., February 11, 2005; 280(6): 4578 - 4584. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Foresti, M. Hoque, D. Monti, C. J. Green, and R. Motterlini Differential Activation of Heme Oxygenase-1 by Chalcones and Rosolic Acid in Endothelial Cells J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 686 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ben-Dor, M. Steiner, L. Gheber, M. Danilenko, N. Dubi, K. Linnewiel, A. Zick, Y. Sharoni, and J. Levy Carotenoids activate the antioxidant response element transcription system Mol. Cancer Ther., January 1, 2005; 4(1): 177 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A.B. Joosten, R. L. Smeets, M. I. Koenders, L. A.M. van den Bersselaar, M. M.A. Helsen, B. Oppers-Walgreen, E. Lubberts, Y. Iwakura, F. A.J. van de Loo, and W. B. van den Berg Interleukin-18 Promotes Joint Inflammation and Induces Interleukin-1-Driven Cartilage Destruction Am. J. Pathol., September 1, 2004; 165(3): 959 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. I. Rojo, M. Salinas, D. Martin, R. Perona, and A. Cuadrado Regulation of Cu/Zn-Superoxide Dismutase Expression via the Phosphatidylinositol 3 Kinase/Akt Pathway and Nuclear Factor-{kappa}B J. Neurosci., August 18, 2004; 24(33): 7324 - 7334. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |