QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (47) Citing Articles via Google Scholar Google Scholar Articles by Saito, A. Articles by Chan, P. H. Search for Related Content PubMed PubMed Citation Articles by Saito, A. Articles by Chan, P. H.

 Previous Article  |  Next Article 

The Journal of Neuroscience, March 1, 2003, 23(5):1710

Overexpression of Copper/Zinc Superoxide Dismutase in Transgenic Mice Protects against Neuronal Cell Death after Transient Focal Ischemia by Blocking Activation of the Bad Cell Death Signaling Pathway

Atsushi Saito, Takeshi Hayashi, Shuzo Okuno, Michel Ferrand-Drake, and Pak H. Chan

Department of Neurosurgery, Department of Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine, Stanford, California 94305-5487

The Bad signaling pathway contributes to the regulation of apoptosis after a variety of cell death stimuli, and Bad plays a key role in determining cell death or survival. We have reported that overexpression of copper/zinc superoxide dismutase (SOD1) reduces apoptotic cell death after transient focal cerebral ischemia (tFCI). However, both the role of the Bad pathway after tFCI and the role of oxygen free radicals in the regulation of apoptosis remain unknown. To clarify these issues, we used an in vivo tFCI model of SOD1 transgenic mice and wild-type mice. Moreover, to examine the role of protein kinase A (PKA) in the Bad pathway after tFCI, we administered the PKA inhibitor, H89, into the mouse brain after tFCI. Immunohistochemistry and Western blot analysis showed that dephosphorylation and translocation of Bad were detected early after tFCI and that they were promoted by H89 treatment but prevented by SOD1. Coimmunoprecipitation revealed that the dimerization of Bad progressed with 14-3-3 (Bad/14-3-3) and with Bcl-x_L (Bad/Bcl-x_L) after tFCI. Moreover, Bad/14-3-3 was prevented by H89 treatment but promoted by SOD1. Bad/Bcl-x_L was prevented by SOD1 but promoted by H89 treatment. A cell death assay revealed that apoptotic-related DNA fragmentation was aggravated by H89 treatment but reduced by SOD1. These results suggest that the Bad pathway mediated by PKA is involved in apoptotic cell death after tFCI and that overexpression of SOD1 may attenuate this apoptotic cell death.

Key words: cerebral ischemia; apoptosis; Bad; Bcl-x_L; 14-3-3; superoxide

---

Copyright © 2003 Society for Neuroscience  0270-6474/03/2351710-09$05.00/0

This article has been cited by other articles:

				B. R.S. Broughton, D. C. Reutens, and C. G. Sobey Apoptotic Mechanisms After Cerebral Ischemia Stroke, May 1, 2009; 40(5): e331 - e339. [Abstract] [Full Text] [PDF]

				C. S. Lobsiger, S. Boillee, M. McAlonis-Downes, A. M. Khan, M. L. Feltri, K. Yamanaka, and D. W. Cleveland Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice PNAS, March 17, 2009; 106(11): 4465 - 4470. [Abstract] [Full Text] [PDF]

				T. Tsubokawa, V. Jadhav, I. Solaroglu, Y. Shiokawa, Y. Konishi, and J. H. Zhang Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats Stroke, March 1, 2007; 38(3): 1057 - 1062. [Abstract] [Full Text] [PDF]

				H. Endo, H. Kamada, C. Nito, T. Nishi, and P. H. Chan Mitochondrial translocation of p53 mediates release of cytochrome c and hippocampal CA1 neuronal death after transient global cerebral ischemia in rats. J. Neurosci., July 26, 2006; 26(30): 7974 - 7983. [Abstract] [Full Text] [PDF]

				A. Saito, T. Hayashi, S. Okuno, T. Nishi, and P. H. Chan Modulation of Proline-Rich Akt Substrate Survival Signaling Pathways by Oxidative Stress in Mouse Brains After Transient Focal Cerebral Ischemia Stroke, February 1, 2006; 37(2): 513 - 517. [Abstract] [Full Text] [PDF]

				J. Liu, P. Narasimhan, F. Yu, and P. H. Chan Neuroprotection by Hypoxic Preconditioning Involves Oxidative Stress-Mediated Expression of Hypoxia-Inducible Factor and Erythropoietin Stroke, June 1, 2005; 36(6): 1264 - 1269. [Abstract] [Full Text] [PDF]

				A. Saito, T. Hayashi, S. Okuno, T. Nishi, and P. H. Chan Oxidative Stress Affects the Integrin-Linked Kinase Signaling Pathway After Transient Focal Cerebral Ischemia Stroke, November 1, 2004; 35(11): 2560 - 2565. [Abstract] [Full Text] [PDF]

				P. H. Chan Future Targets and Cascades for Neuroprotective Strategies Stroke, November 1, 2004; 35(11_suppl_1): 2748 - 2750. [Abstract] [Full Text] [PDF]

				D. S. Warner, H. Sheng, and I. Batinic-Haberle Oxidants, antioxidants and the ischemic brain J. Exp. Biol., August 15, 2004; 207(18): 3221 - 3231. [Abstract] [Full Text] [PDF]

				M. D. Johnson, L.-R. Yu, T. P. Conrads, Y. Kinoshita, T. Uo, J. D. Matthews, S.-W. Lee, R. D. Smith, T. D. Veenstra, and R. S. Morrison Proteome Analysis of DNA Damage-induced Neuronal Death Using High Throughput Mass Spectrometry J. Biol. Chem., June 18, 2004; 279(25): 26685 - 26697. [Abstract] [Full Text] [PDF]

				A. Saito, T. Hayashi, S. Okuno, T. Nishi, and P. H. Chan Oxidative Stress Is Associated With XIAP and Smac/DIABLO Signaling Pathways in Mouse Brains After Transient Focal Cerebral Ischemia Stroke, June 1, 2004; 35(6): 1443 - 1448. [Abstract] [Full Text] [PDF]

				A. Saito, P. Narasimhan, T. Hayashi, S. Okuno, M. Ferrand-Drake, and P. H. Chan Neuroprotective Role of a Proline-Rich Akt Substrate in Apoptotic Neuronal Cell Death after Stroke: Relationships with Nerve Growth Factor J. Neurosci., February 18, 2004; 24(7): 1584 - 1593. [Abstract] [Full Text] [PDF]

				A. Kamsler and M. Segal Paradoxical Actions of Hydrogen Peroxide on Long-Term Potentiation in Transgenic Superoxide Dismutase-1 Mice J. Neurosci., November 12, 2003; 23(32): 10359 - 10367. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help