WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience Serious about science: Serious about timing
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, February 11, 2004, 24(6):1350-1357; doi:10.1523/JNEUROSCI.1596-03.2004

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (39)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Romera, C.
Right arrow Articles by Moro, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Romera, C.
Right arrow Articles by Moro, M. A.

 Previous Article  |  Next Article 

Neurobiology of Disease
In Vitro Ischemic Tolerance Involves Upregulation of Glutamate Transport Partly Mediated by the TACE/ADAM17-Tumor Necrosis Factor-{alpha} Pathway

Cristina Romera,1 Olivia Hurtado,1 Sofia H. Botella,1 Ignacio Lizasoain,1 Antonio Cárdenas,1 Paz Fernández-Tomé,2 Juan C. Leza,1 Pedro Lorenzo,1 and Maria A. Moro1

1Departamento de Farmacología and 2Instituto Mixto de Farmacología-Toxicología, Consejo Superior de Investigaciones Científicas, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain

A short ischemic event [ischemic preconditioning (IPC)] can result in a subsequent resistance to severe ischemic injury (ischemic tolerance). Although tumor necrosis factor-{alpha} (TNF-{alpha}) contributes to the brain damage found after cerebral ischemia, its expression and neuroprotective role in models of IPC have also been described. Regarding the role of TNF-{alpha} convertase (TACE/ADAM17), we have recently shown its upregulation in rat brain after IPC induced by transient middle cerebral artery occlusion and that subsequent TNF-{alpha} release accounts for at least part of the neuroprotection found in this model. We have now used an in vitro model of IPC using rat cortical cultures exposed to sublethal oxygen-glucose deprivation (OGD) to investigate TACE expression and activity after IPC and the subsequent mechanisms of ischemic tolerance. OGD-induced cell death was significantly reduced in cells exposed to IPC by sublethal OGD 24 hr before, an effect that was inhibited by the TACE inhibitor BB3103 (1 µM) and anti-TNF-{alpha} antibody (2 µg/ml) and that was mimicked by TNF-{alpha} (10 pg/ml) preincubation. Western blot analysis showed that TACE expression is increased after IPC. IPC caused TNF-{alpha} release, an effect that was blocked by the selective TACE inhibitor BB-3103. In addition, IPC diminished the increase in extracellular glutamate caused by OGD and increased cellular glutamate uptake and expression of EAAT2 and EAAT3 glutamate transporters; however, only EAAT3 upregulation was mediated by increased TNF-{alpha}. These data demonstrate that neuroprotection induced by IPC involves upregulation of glutamate uptake partly mediated by TACE overexpression.

Key words: cerebral ischemia; ischemic preconditioning; transporters; neuroprotection; stroke; TNF-{alpha}

Received July 2, 2003; revised December 2, 2003; accepted December 4, 2003.




This article has been cited by other articles:


Home page
 Physiol. Rev.Home page
T. P. Obrenovitch
Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia
Physiol Rev, January 1, 2008; 88(1): 211 - 247.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Domercq, M. V. Sanchez-Gomez, C. Sherwin, E. Etxebarria, R. Fern, and C. Matute
System xc- and Glutamate Transporter Inhibition Mediates Microglial Toxicity to Oligodendrocytes
J. Immunol., May 15, 2007; 178(10): 6549 - 6556.
[Abstract] [Full Text] [PDF]

Home page
 StrokeHome page
K. Chu, S.-T. Lee, D.-I. Sinn, S.-Y. Ko, E.-H. Kim, J.-M. Kim, S.-J. Kim, D.-K. Park, K.-H. Jung, E.-C. Song, et al.
Pharmacological Induction of Ischemic Tolerance by Glutamate Transporter-1 (EAAT2) Upregulation
Stroke, January 1, 2007; 38(1): 177 - 182.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
J. Mallolas, O. Hurtado, M. Castellanos, M. Blanco, T. Sobrino, J. Serena, J. Vivancos, J. Castillo, I. Lizasoain, M. A. Moro, et al.
A polymorphism in the EAAT2 promoter is associated with higher glutamate concentrations and higher frequency of progressing stroke
J. Exp. Med., March 20, 2006; 203(3): 711 - 717.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
L. Armstrong, S. I. H. Godinho, K. M. Uppington, H. A. Whittington, and A. B. Millar
Contribution of TNF-{alpha} Converting Enzyme and Proteinase-3 to TNF-{alpha} Processing in Human Alveolar Macrophages
Am. J. Respir. Cell Mol. Biol., February 1, 2006; 34(2): 219 - 225.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
T. Kaneko, K. Yokoyama, and K. Makita
Late preconditioning with isoflurane in cultured rat cortical neurones
Br. J. Anaesth., November 1, 2005; 95(5): 662 - 668.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Bour-Jordan, H. L. Thompson, and J. A. Bluestone
Distinct Effector Mechanisms in the Development of Autoimmune Neuropathy versus Diabetes in Nonobese Diabetic Mice
J. Immunol., November 1, 2005; 175(9): 5649 - 5655.
[Abstract] [Full Text] [PDF]


-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2008 by Society for Neuroscience ONLINE ISSN: 1529-2401
-