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MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia
Open accessAbstract
The MEK1 ( M AP kinase/ E RK k inase)/ERK ( e xtracellular-signal- r esponsive k inase) pathway has been implicated in cell growth and differentiation [Seger, R. & Krebs, E. G. (1995) FASEB J. 9, 726–735]. Here we show that the MEK/ERK pathway is activated during focal cerebral ischemia and may play a role in inducing damage. Treatment of mice 30 min before ischemia with the MEK1-specific inhibitor PD98059 [Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T. & Saltiel, A. R. (1995) J. Biol. Chem. 270, 27489–27494] reduces focal infarct volume at 22 hr after ischemia by 55% after transient occlusion of the middle cerebral artery. This is accompanied by a reduction in phospho-ERK1/2 immunohistochemical staining. MEK1 inhibition also results in reduced brain damage 72 hr after ischemia, with focal infarct volume reduced by 36%. This study indicates that the MEK1/ERK pathway contributes to brain injury during focal cerebral ischemia and that PD98059, a MEK1-specific antagonist, is a potent neuroprotective agent.
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Cited by
Tikka, T., Fiebich, B. L., Goldsteins, G., Keinänen, R., & Koistinaho, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02580.2001 · Cited by 958
Stanciu, M., Wang, Y., Kentor, R., Burke, N., Watkins, S., Kress, G., Reynolds, I., Klann, E., Angiolieri, M. R., Johnson, J. W., et al. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.16.12200 · Cited by 539
The Role of PI3K/Akt and ERK in Neurodegenerative Disorders
Rai, S. N., Dilnashin, H., Birla, H., Singh, S. S., Zahra, W., Rathore, A. S., Singh, B. K., & Singh, S. P. (2019) · Neurotoxicity Research · doi:10.1007/s12640-019-0003-y · Cited by 478
Mandel, S., Weinreb, O., Amit, T., & Youdim, M. B. H. (2004) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02291.x · Cited by 377
A Death-Promoting Role for Extracellular Signal-Regulated Kinase
Zhuang, S., & Schnellmann, R. G. (2006) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.107367 · Cited by 355
Metadata
- Authors
- Alessandrini, A., Namura, S., Moskowitz, M. A., & Bonventre, J. V.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-10-26
- Volume
- 96
- Issue
- 22
- Pages
- 12866-12869
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2043033966
- Cited by
- 464
- References
- 0
- FWCI
- 22.20
- Type
- journal article
- Language
- en
- Open access
- green
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- Alessandrini, A., Namura, S., Moskowitz, M. A., & Bonventre, J. V. (1999). MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.96.22.12866
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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