 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, November 15, 1999, 19(22):9821-9830
Protection from Oxidative Stress-Induced Apoptosis in Cortical Neuronal Cultures by Iron Chelators Is Associated with Enhanced DNA Binding of Hypoxia-Inducible Factor-1 and ATF-1/CREB and Increased Expression of Glycolytic Enzymes, p21waf1/cip1, and Erythropoietin
Khalequz Zaman1, Hoon Ryu1, David Hall1, Kevin O'Donovan5, Kuo-I Lin1, Matthew P. Miller1, John C. Marquis3, Jay M. Baraban5, 7, Gregg L. Semenza4, 6, and Rajiv R. Ratan1, 2 1 Department of Neurology and 2 Program in Neuroscience, Harvard Medical School and The Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, 3 Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts, and 4 Institute of Genetic Medicine and Departments of 5 Neuroscience, 6 Pediatrics, and 7 Psychiatry and Behavioral Science, Johns Hopkins University School of Medicine, Baltimore, Maryland
Iron chelators are pluripotent neuronal antiapoptotic agents that have been shown to enhance metabolic recovery in cerebral ischemia models. The precise mechanism(s) by which these agents exert their effects remains unclear. Recent studies have demonstrated that iron chelators activate a hypoxia signal transduction pathway in non-neuronal cells that culminates in the stabilization of the transcriptional activator hypoxia-inducible factor-1 (HIF-1) and increased expression of gene products that mediate hypoxic adaptation. We examined the hypothesis that iron chelators prevent oxidative stress-induced death in cortical neuronal cultures by inducing expression of HIF-1 and its target genes. We report that the structurally distinct iron chelators deferoxamine mesylate and mimosine prevent apoptosis induced by glutathione depletion and oxidative stress in embryonic cortical neuronal cultures. The protective effects of iron chelators are correlated with their ability to enhance DNA binding of HIF-1 and activating transcription factor 1(ATF-1)/cAMP response element-binding protein (CREB) to the hypoxia response element in cortical cultures and the H19-7 hippocampal neuronal cell line. We show that mRNA, protein, and/or activity levels for genes whose expression is known to be regulated by HIF-1, including glycolytic enzymes, p21waf1/cip1, and erythropoietin, are increased in cortical neuronal cultures in response to iron chelator treatment. Finally, we demonstrate that cobalt chloride, which also activates HIF-1 and ATF-1/CREB in cortical cultures, also prevents oxidative stress-induced death in these cells. Altogether, these results suggest that iron chelators exert their neuroprotective effects, in part, by activating a signal transduction pathway leading to increased expression of genes known to compensate for hypoxic or oxidative stress.
Key words: iron chelators; oxidative stress; glutathione; apoptosis; HIF-1; ATF-1/CREB
Copyright © 1999 Society for Neuroscience 0270-6474/99/19229821-10$05.00/0
This article has been cited by other articles:
A. Siddiq, L. R. Aminova, C. M. Troy, K. Suh, Z. Messer, G. L. Semenza, and R. R. Ratan
Selective Inhibition of Hypoxia-Inducible Factor (HIF) Prolyl-Hydroxylase 1 Mediates Neuroprotection against Normoxic Oxidative Death via HIF- and CREB-Independent Pathways
J. Neurosci., July 8, 2009; 29(27): 8828 - 8838.
[Abstract] [Full Text] [PDF]
D. K. Slonim, K. Koide, K. L. Johnson, U. Tantravahi, J. M. Cowan, Z. Jarrah, and D. W. Bianchi
Functional genomic analysis of amniotic fluid cell-free mRNA suggests that oxidative stress is significant in Down syndrome fetuses
PNAS, June 9, 2009; 106(23): 9425 - 9429.
[Abstract] [Full Text] [PDF]
M. Selim
Deferoxamine Mesylate: A New Hope for Intracerebral Hemorrhage: From Bench to Clinical Trials
Stroke, March 1, 2009; 40(3_suppl_1): S90 - S91.
[Abstract] [Full Text] [PDF]
R. R. Ratan and M. Noble
Novel Multi-Modal Strategies to Promote Brain and Spinal Cord Injury Recovery
Stroke, March 1, 2009; 40(3_suppl_1): S130 - S132.
[Abstract] [Full Text] [PDF]
Y. Ho, R. Samarasinghe, M. E. Knoch, M. Lewis, E. Aizenman, and D. B. DeFranco
Selective Inhibition of Mitogen-Activated Protein Kinase Phosphatases by Zinc Accounts for Extracellular Signal-Regulated Kinase 1/2-Dependent Oxidative Neuronal Cell Death
Mol. Pharmacol., October 1, 2008; 74(4): 1141 - 1151.
[Abstract] [Full Text] [PDF]
T. Amit, Y. Avramovich-Tirosh, M. B. H. Youdim, and S. Mandel
Targeting multiple Alzheimer's disease etiologies with multimodal neuroprotective and neurorestorative iron chelators
FASEB J, May 1, 2008; 22(5): 1296 - 1305.
[Abstract] [Full Text] [PDF]
K. Iwasaki, K. Hailemariam, and Y. Tsuji
PIAS3 Interacts with ATF1 and Regulates the Human Ferritin H Gene through an Antioxidant-responsive Element
J. Biol. Chem., August 3, 2007; 282(31): 22335 - 22343.
[Abstract] [Full Text] [PDF]
O. Baranova, L. F. Miranda, P. Pichiule, I. Dragatsis, R. S. Johnson, and J. C. Chavez
Neuron-Specific Inactivation of the Hypoxia Inducible Factor 1{alpha} Increases Brain Injury in a Mouse Model of Transient Focal Cerebral Ischemia
J. Neurosci., June 6, 2007; 27(23): 6320 - 6332.
[Abstract] [Full Text] [PDF]
L. Zhong, J. Bradley, W. Schubert, E. Ahmed, A. P. Adamis, D. T. Shima, G. S. Robinson, and Y.-S. Ng
Erythropoietin Promotes Survival of Retinal Ganglion Cells in DBA/2J Glaucoma Mice
Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1212 - 1218.
[Abstract] [Full Text] [PDF]
R. Vene, G. Arena, A. Poggi, C. D'Arrigo, M. Mormino, D. M. Noonan, A. Albini, and F. Tosetti
Novel cell death pathways induced by N-(4-hydroxyphenyl)retinamide: therapeutic implications
Mol. Cancer Ther., January 1, 2007; 6(1): 286 - 298.
[Abstract] [Full Text] [PDF]
K. E. Jie, M. C. Verhaar, M.-J. M. Cramer, K. van der Putten, C. A. J. M. Gaillard, P. A. Doevendans, H. A. Koomans, J. A. Joles, and B. Braam
Erythropoietin and the cardiorenal syndrome: cellular mechanisms on the cardiorenal connectors
Am J Physiol Renal Physiol, November 1, 2006; 291(5): F932 - F944.
[Abstract] [Full Text] [PDF]
M. I. Koukourakis, A. Giatromanolaki, E. Sivridis, K. C. Gatter, and A. L. Harris
Lactate Dehydrogenase 5 Expression in Operable Colorectal Cancer: Strong Association With Survival and Activated Vascular Endothelial Growth Factor Pathway--A Report of the Tumour Angiogenesis Research Group
J. Clin. Oncol., September 10, 2006; 24(26): 4301 - 4308.
[Abstract] [Full Text] [PDF]
A M Emara, R S El Kelany, and K A Moustafa
Comparative study of the protective effect between deferoxamine and deferiprone on chronic iron overload induced cardiotoxicity in rats
Human and Experimental Toxicology, July 1, 2006; 25(7): 375 - 385.
[Abstract] [PDF]
J. Petrak, D. Myslivcova, P. Man, R. Cmejla, J. Cmejlova, and D. Vyoral
Proteomic analysis of iron overload in human hepatoma cells
Am J Physiol Gastrointest Liver Physiol, May 1, 2006; 290(5): G1059 - G1066.
[Abstract] [Full Text] [PDF]
S. Bissoon-Haqqani, T. Moyana, D. Jonker, J. A. Maroun, and H. C. Birnboim
Nuclear Expression of Thymidylate Synthase in Colorectal Cancer Cell Lines and Clinical Samples
J. Histochem. Cytochem., January 1, 2006; 54(1): 19 - 29.
[Abstract] [Full Text] [PDF]
A. Siddiq, I. A. Ayoub, J. C. Chavez, L. Aminova, S. Shah, J. C. LaManna, S. M. Patton, J. R. Connor, R. A. Cherny, I. Volitakis, et al.
Hypoxia-inducible Factor Prolyl 4-Hydroxylase Inhibition: A TARGET FOR NEUROPROTECTION IN THE CENTRAL NERVOUS SYSTEM
J. Biol. Chem., December 16, 2005; 280(50): 41732 - 41743.
[Abstract] [Full Text] [PDF]
H. Ryu, J. Lee, S. Impey, R. R. Ratan, and R. J. Ferrante
Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons
PNAS, September 27, 2005; 102(39): 13915 - 13920.
[Abstract] [Full Text] [PDF]
A. J. Lazarowski, H. J. Garcia Rivello, G. L. Vera Janavel, L. A. Cuniberti, P. M. Cabeza Meckert, G. G. Yannarelli, A. Mele, A. J. Crottogini, and R. P. Laguens
Cardiomyocytes of Chronically Ischemic Pig Hearts Express the MDR-1 Gene-encoded P-glycoprotein
J. Histochem. Cytochem., July 1, 2005; 53(7): 845 - 850.
[Abstract] [Full Text] [PDF]
L. Xie, R. S. Johnson, and R. S. Freeman
Inhibition of NGF deprivation-induced death by low oxygen involves suppression of BIMEL and activation of HIF-1
J. Cell Biol., March 14, 2005; 168(6): 911 - 920.
[Abstract] [Full Text] [PDF]
L. R. Aminova, J. C. Chavez, J. Lee, H. Ryu, A. Kung, J. C. LaManna, and R. R. Ratan
Prosurvival and Prodeath Effects of Hypoxia-inducible Factor-1{alpha} Stabilization in a Murine Hippocampal Cell Line
J. Biol. Chem., February 4, 2005; 280(5): 3996 - 4003.
[Abstract] [Full Text] [PDF]
A. Giatromanolaki, M. I. Koukourakis, C. Simopoulos, A. Polychronidis, K. C. Gatter, A. L. Harris, and E. Sivridis
c-erbB-2 Related Aggressiveness in Breast Cancer Is Hypoxia Inducible Factor-1{alpha} Dependent
Clin. Cancer Res., December 1, 2004; 10(23): 7972 - 7977.
[Abstract] [Full Text] [PDF]
R. R. Ratan, A. Siddiq, L. Aminova, P. S. Lange, B. Langley, I. Ayoub, J. Gensert, and J. Chavez
Translation of Ischemic Preconditioning to the Patient: Prolyl Hydroxylase Inhibition and Hypoxia Inducible Factor-1 as Novel Targets for Stroke Therapy
Stroke, November 1, 2004; 35(11_suppl_1): 2687 - 2689.
[Abstract] [Full Text] [PDF]
M.-J. Lee, J.-Y. Kim, K. Suk, and J.-H. Park
Identification of the Hypoxia-Inducible Factor 1{alpha}-Responsive HGTD-P Gene as a Mediator in the Mitochondrial Apoptotic Pathway
Mol. Cell. Biol., May 1, 2004; 24(9): 3918 - 3927.
[Abstract] [Full Text] [PDF]
A. Suzuki, J. Lu, G.-i. Kusakai, A. Kishimoto, T. Ogura, and H. Esumi
ARK5 Is a Tumor Invasion-Associated Factor Downstream of Akt Signaling
Mol. Cell. Biol., April 15, 2004; 24(8): 3526 - 3535.
[Abstract] [Full Text] [PDF]
G. Grasso, A. Sfacteria, A. Cerami, and M. Brines
Erythropoietin as a Tissue-Protective Cytokine in Brain Injury: What Do We Know and Where Do We Go?
Neuroscientist, April 1, 2004; 10(2): 93 - 98.
[Abstract] [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. H. Cheong, D. Bannon, L. Olivi, Y. Kim, and J. Bressler
Different Mechanisms Mediate Uptake of Lead in a Rat Astroglial Cell Line
Toxicol. Sci., February 1, 2004; 77(2): 334 - 340.
[Abstract] [Full Text] [PDF]
J.-Y. Kim, H.-J. Ahn, J.-H. Ryu, K. Suk, and J.-H. Park
BH3-only Protein Noxa Is a Mediator of Hypoxic Cell Death Induced by Hypoxia-inducible Factor 1{alpha}
J. Exp. Med., January 5, 2004; 199(1): 113 - 124.
[Abstract] [Full Text] [PDF]
H. Ryu, J. Lee, K. Zaman, J. Kubilis, R. J. Ferrante, B. D. Ross, R. Neve, and R. R. Ratan
Sp1 and Sp3 Are Oxidative Stress-Inducible, Antideath Transcription Factors in Cortical Neurons
J. Neurosci., May 1, 2003; 23(9): 3597 - 3606.
[Abstract] [Full Text] [PDF]
H. Ryu, J. Lee, B. A. Olofsson, A. Mwidau, A. Dedeoglu, M. Escudero, E. Flemington, J. Azizkhan-Clifford, R. J. Ferrante, and R. R. Ratan
Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway
PNAS, April 1, 2003; 100(7): 4281 - 4286.
[Abstract] [Full Text] [PDF]
S. Ahmad, A. Ahmad, E. Gerasimovskaya, K. R. Stenmark, C. B. Allen, and C. W. White
Hypoxia Protects Human Lung Microvascular Endothelial and Epithelial-like Cells against Oxygen Toxicity: Role of Phosphatidylinositol 3-Kinase
Am. J. Respir. Cell Mol. Biol., February 1, 2003; 28(2): 179 - 187.
[Abstract] [Full Text] [PDF]
K. Ruscher, D. Freyer, M. Karsch, N. Isaev, D. Megow, B. Sawitzki, J. Priller, U. Dirnagl, and A. Meisel
Erythropoietin Is a Paracrine Mediator of Ischemic Tolerance in the Brain: Evidence from an In Vitro Model
J. Neurosci., December 1, 2002; 22(23): 10291 - 10301.
[Abstract] [Full Text] [PDF]
J. C. Chavez and J. C. LaManna
Activation of Hypoxia-Inducible Factor-1 in the Rat Cerebral Cortex after Transient Global Ischemia: Potential Role of Insulin-Like Growth Factor-1
J. Neurosci., October 15, 2002; 22(20): 8922 - 8931.
[Abstract] [Full Text] [PDF]
I. N. KRASNOVA, M. T. MCCOY, B. LADENHEIM, and J. L. CADET
cDNA array analysis of gene expression profiles in the striata of wild-type and Cu/Zn superoxide dismutase transgenic mice treated with neurotoxic doses of amphetamine
FASEB J, September 1, 2002; 16(11): 1379 - 1388.
[Abstract] [Full Text] [PDF]
T. Shoshani, A. Faerman, I. Mett, E. Zelin, T. Tenne, S. Gorodin, Y. Moshel, S. Elbaz, A. Budanov, A. Chajut, et al.
Identification of a Novel Hypoxia-Inducible Factor 1-Responsive Gene, RTP801, Involved in Apoptosis
Mol. Cell. Biol., April 1, 2002; 22(7): 2283 - 2293.
[Abstract] [Full Text] [PDF]
E. Y. Chen, N. M. Mazure, J. A. Cooper, and A. J. Giaccia
Hypoxia Activates a Platelet-derived Growth Factor Receptor/Phosphatidylinositol 3-Kinase/Akt Pathway That Results in Glycogen Synthase Kinase-3 Inactivation
Cancer Res., March 1, 2001; 61(6): 2429 - 2433.
[Abstract] [Full Text]
K. Izuishi, K. Kato, T. Ogura, T. Kinoshita, and H. Esumi
Remarkable Tolerance of Tumor Cells to Nutrient Deprivation: Possible New Biochemical Target for Cancer Therapy
Cancer Res., November 1, 2000; 60(21): 6201 - 6207.
[Abstract] [Full Text]
L. Studer, M. Csete, S.-H. Lee, N. Kabbani, J. Walikonis, B. Wold, and R. McKay
Enhanced Proliferation, Survival, and Dopaminergic Differentiation of CNS Precursors in Lowered Oxygen
J. Neurosci., October 1, 2000; 20(19): 7377 - 7383.
[Abstract] [Full Text] [PDF]
M. Ogilvie, X. Yu, V. Nicolas-Metral, S. M. Pulido, C. Liu, U. T. Ruegg, and C. T. Noguchi
Erythropoietin Stimulates Proliferation and Interferes with Differentiation of Myoblasts
J. Biol. Chem., December 8, 2000; 275(50): 39754 - 39761.
[Abstract] [Full Text] [PDF]
F. H. Agani, P. Pichiule, J. C. Chavez, and J. C. LaManna
The Role of Mitochondria in the Regulation of Hypoxia-inducible Factor 1 Expression during Hypoxia
J. Biol. Chem., November 10, 2000; 275(46): 35863 - 35867.
[Abstract] [Full Text] [PDF]
M. Alvarez-Tejado, S. Naranjo-Suarez, C. Jimenez, A. C. Carrera, M. O. Landazuri, and L. del Peso
Hypoxia Induces the Activation of the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway in PC12 Cells. PROTECTIVE ROLE IN APOPTOSIS
J. Biol. Chem., June 15, 2001; 276(25): 22368 - 22374.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|