 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, February 4, 2004, 24(5):1101-1112; doi:10.1523/JNEUROSCI.3817-03.2004
Previous Article | Next Article
Cellular/Molecular
Nuclear Factor E2-Related Factor 2-Dependent Antioxidant Response Element Activation by tert-Butylhydroquinone and Sulforaphane Occurring Preferentially in Astrocytes Conditions Neurons against Oxidative Insult
Andrew D. Kraft,1 Delinda A. Johnson,1 andJeffrey A. Johnson1,2,3 1School of Pharmacy, 2Waisman Center, and 3Molecular and Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin 53705
Binding of the transcription factor nuclear factor E2-related factor 2 (Nrf2) to the antioxidant response element (ARE) in neural cells results in the induction of a battery of genes that can coordinate a protective response against a variety of oxidative stressors. In this study, tert-butylhydroquinone (tBHQ) and sulforaphane were used as activators of this pathway. Consistent with previous studies, treatment of primary cortical cultures from ARE reporter mice revealed selective promoter activity in astrocytes. This activation protected neurons from hydrogen peroxide and nonexcitotoxic glutamate toxicity. tBHQ treatment of cultures from Nrf2 knock-out animals resulted in neither ARE activation nor neuroprotection. By reintroducing Nrf2 via infection with a replication-deficient adenovirus (ad), both the genetic response and neuroprotection were rescued. Conversely, infection with adenovirus encoding dominant-negative (DN) Nrf2 (ad-DN-Nrf2) or pretreatment with the selective phosphatidylinositol-3 kinase inhibitor LY294002
inhibited the tBHQ-mediated promoter response and corresponding neuroprotection. Interestingly, the adenoviral infection showed a high selectivity for astrocytes over neurons. In an attempt to reveal some of the cell type-specific changes resulting from ARE activation, cultures were infected with adenovirus encoding green fluorescent protein (GFP) (ad-GFP) or ad-DN-Nrf2 (containing GFP) before tBHQ treatment. A glia-enriched population of GFP-infected cells was then isolated from a population of uninfected neurons using cell-sorting technology. Microarray analysis was used to evaluate potential glial versus neuron-specific contributions to the neuroprotective effects of ARE activation and Nrf2 dependence. Strikingly, the change in neuronal gene expression after tBHQ treatment was dependent on Nrf2 activity in the astrocytes. This suggests that Nrf2-dependent genetic changes alter neuron–glia interactions resulting in neuroprotection.
Key words: antioxidant response element; oxidative stress; neuroprotection; Nrf2; microarray; sulforaphane; glia–neuron interaction; cell sorting
Received Aug 15, 2003; revised November 18, 2003; accepted November 20, 2003.
This article has been cited by other articles:
K.-H. Kim, J.-Y. Jeong, Y.-J. Surh, and K.-W. Kim
Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes
Nucleic Acids Res., October 28, 2009; (2009) gkp865v1.
[Abstract] [Full Text] [PDF]
F. Ali, M. Zakkar, K. Karu, E. A. Lidington, S. S. Hamdulay, J. J. Boyle, M. Zloh, A. Bauer, D. O. Haskard, P. C. Evans, et al.
Induction of the Cytoprotective Enzyme Heme Oxygenase-1 by Statins Is Enhanced in Vascular Endothelium Exposed to Laminar Shear Stress and Impaired by Disturbed Flow
J. Biol. Chem., July 10, 2009; 284(28): 18882 - 18892.
[Abstract] [Full Text] [PDF]
T. Nguyen, P. Nioi, and C. B. Pickett
The Nrf2-Antioxidant Response Element Signaling Pathway and Its Activation by Oxidative Stress
J. Biol. Chem., May 15, 2009; 284(20): 13291 - 13295.
[Abstract] [Full Text] [PDF]
S. A. Reisman, I. L. Csanaky, R. L. Yeager, and C. D. Klaassen
Nrf2 Activation Enhances Biliary Excretion of Sulfobromophthalein by Inducing Glutathione-S-Transferase Activity
Toxicol. Sci., May 1, 2009; 109(1): 24 - 30.
[Abstract] [Full Text] [PDF]
P.-C. Chen, M. R. Vargas, A. K. Pani, R. J. Smeyne, D. A. Johnson, Y. W. Kan, and J. A. Johnson
Nrf2-mediated neuroprotection in the MPTP mouse model of Parkinson's disease: Critical role for the astrocyte
PNAS, February 24, 2009; 106(8): 2933 - 2938.
[Abstract] [Full Text] [PDF]
M. R. Vargas, D. A. Johnson, D. W. Sirkis, A. Messing, and J. A. Johnson
Nrf2 Activation in Astrocytes Protects against Neurodegeneration in Mouse Models of Familial Amyotrophic Lateral Sclerosis
J. Neurosci., December 10, 2008; 28(50): 13574 - 13581.
[Abstract] [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]
X. Zhao, G. Sun, J. Zhang, R. Strong, P. K. Dash, Y. W. Kan, J. C. Grotta, and J. Aronowski
Transcription Factor Nrf2 Protects the Brain From Damage Produced by Intracerebral Hemorrhage
Stroke, December 1, 2007; 38(12): 3280 - 3286.
[Abstract] [Full Text] [PDF]
N. Onishchenko, C. Tamm, M. Vahter, T. Hokfelt, J. A. Johnson, D. A. Johnson, and S. Ceccatelli
Developmental Exposure to Methylmercury Alters Learning and Induces Depression-like Behavior in Male Mice
Toxicol. Sci., June 1, 2007; 97(2): 428 - 437.
[Abstract] [Full Text] [PDF]
J. M. Han, Y. J. Lee, S. Y. Lee, E. M. Kim, Y. Moon, H. W. Kim, and O. Hwang
Protective Effect of Sulforaphane against Dopaminergic Cell Death
J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 249 - 256.
[Abstract] [Full Text] [PDF]
Y. Liu, J. T. Kern, J. R. Walker, J. A. Johnson, P. G. Schultz, and H. Luesch
A genomic screen for activators of the antioxidant response element
PNAS, March 20, 2007; 104(12): 5205 - 5210.
[Abstract] [Full Text] [PDF]
X. Sun, A. Y. Shih, H. C. Johannssen, H. Erb, P. Li, and T. H. Murphy
Two-photon Imaging of Glutathione Levels in Intact Brain Indicates Enhanced Redox Buffering in Developing Neurons and Cells at the Cerebrospinal Fluid and Blood-Brain Interface
J. Biol. Chem., June 23, 2006; 281(25): 17420 - 17431.
[Abstract] [Full Text] [PDF]
T. Satoh, S.-i. Okamoto, J. Cui, Y. Watanabe, K. Furuta, M. Suzuki, K. Tohyama, and S. A. Lipton
From the Cover: Activation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers
PNAS, January 17, 2006; 103(3): 768 - 773.
[Abstract] [Full Text] [PDF]
A. Y. Shih, P. Li, and T. H. Murphy
A Small-Molecule-Inducible Nrf2-Mediated Antioxidant Response Provides Effective Prophylaxis against Cerebral Ischemia In Vivo
J. Neurosci., November 2, 2005; 25(44): 10321 - 10335.
[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]
R. J. Jakel, J. T. Kern, D. A. Johnson, and J. A. Johnson
Induction of the Protective Antioxidant Response Element Pathway by 6-Hydroxydopamine In Vivo and In Vitro
Toxicol. Sci., September 1, 2005; 87(1): 176 - 186.
[Abstract] [Full Text] [PDF]
M. R. Vargas, M. Pehar, P. Cassina, L. Martinez-Palma, J. A. Thompson, J. S. Beckman, and L. Barbeito
Fibroblast Growth Factor-1 Induces Heme Oxygenase-1 via Nuclear Factor Erythroid 2-related Factor 2 (Nrf2) in Spinal Cord Astrocytes: CONSEQUENCES FOR MOTOR NEURON SURVIVAL
J. Biol. Chem., July 8, 2005; 280(27): 25571 - 25579.
[Abstract] [Full Text] [PDF]
J.-M. Lee, J. Li, D. A. Johnson, T. D. Stein, A. D. Kraft, M. J. Calkins, R. J. Jakel, and J. A. Johnson
Nrf2, a multi-organ protector?
FASEB J, July 1, 2005; 19(9): 1061 - 1066.
[Abstract] [Full Text] [PDF]
A. Y. Shih, S. Imbeault, V. Barakauskas, H. Erb, L. Jiang, P. Li, and T. H. Murphy
Induction of the Nrf2-driven Antioxidant Response Confers Neuroprotection during Mitochondrial Stress in Vivo
J. Biol. Chem., June 17, 2005; 280(24): 22925 - 22936.
[Abstract] [Full Text] [PDF]
T. W. P. Devling, C. D. Lindsay, L. I. McLellan, M. McMahon, and J. D. Hayes
Utility of siRNA against Keap1 as a strategy to stimulate a cancer chemopreventive phenotype
PNAS, May 17, 2005; 102(20): 7280 - 7285.
[Abstract] [Full Text] [PDF]
J. Li, M. L. Spletter, and J. A. Johnson
Dissecting tBHQ induced ARE-driven gene expression through long and short oligonucleotide arrays
Physiol Genomics, March 21, 2005; 21(1): 43 - 58.
[Abstract] [Full Text] [PDF]
J. Li, D. Johnson, M. Calkins, L. Wright, C. Svendsen, and J. Johnson
Stabilization of Nrf2 by tBHQ Confers Protection against Oxidative Stress-Induced Cell Death in Human Neural Stem Cells
Toxicol. Sci., February 1, 2005; 83(2): 313 - 328.
[Abstract] [Full Text] [PDF]
M. J. Calkins, R. J. Jakel, D. A. Johnson, K. Chan, Y. W. Kan, and J. A. Johnson
Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription
PNAS, January 4, 2005; 102(1): 244 - 249.
[Abstract] [Full Text] [PDF]
J.-M. Lee, K. Chan, Y. W. Kan, and J. A. Johnson
Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia
PNAS, June 29, 2004; 101(26): 9751 - 9756.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|