MEK and ERK protect hypoxic cortical neurons via phosphorylation of Bad
- PMID: 11796750
- DOI: 10.1046/j.0022-3042.2001.00678.x
MEK and ERK protect hypoxic cortical neurons via phosphorylation of Bad
Abstract
We investigated the role of mitogen-activated protein kinase (MAPK) pathways in hypoxic neuronal injury using primary cultures from murine cerebral cortex. Hypoxia caused the death of approximately 50% of neurons at 16 h and approximately 65% of neurons at 24 h. This was associated with phospho-activation of the MAPK/extracellular signal-regulated kinase (ERK) kinase MEK1/2 and its downstream target ERK1/2, but not p38 MAPK or c-Jun N-terminal kinase (JNK), as detected by western blotting. The MEK1/2 inhibitor, PD98059, increased neuronal death in hypoxic cultures, suggesting that MEK1/2 promotes neuronal survival, whereas the p38 inhibitors, SB202190 and SB203580, had no effect. To identify downstream effects of ERK1/2 that might regulate hypoxic neuronal death, we measured hypoxia-induced phosphorylation of three ERK1/2 targets: the 90-kDa ribosomal protein S6 kinase (RSK), the transcription factor ELK1, and the pro-apoptotic Bcl-2 family protein Bad. We observed increased abundance of inactivated (phospho-)Bad, but no change in phospho-RSK or phospho-ELK1. Moreover, the MEK inhibitor PD98059 reduced phospho-inactivation of Bad in hypoxic cultures. These findings suggest that a cell-survival program involving phospho-activation of MEK1/2 and ERK1/2 and inactivation of Bad is mobilized in hypoxic neurons, and may help to regulate neuronal fate following hypoxic-ischemic injury.
Similar articles
-
Purine nucleosides: endogenous neuroprotectants in hypoxic brain.J Neurochem. 2012 May;121(3):329-42. doi: 10.1111/j.1471-4159.2012.07692.x. Epub 2012 Mar 14. J Neurochem. 2012. PMID: 22335456 Free PMC article. Review.
-
Activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) during hypoxia in cerebral cortical nuclei of guinea pig fetus at term: role of nitric oxide.Neurosci Lett. 2008 Jul 4;439(1):94-9. doi: 10.1016/j.neulet.2008.02.037. Epub 2008 Feb 26. Neurosci Lett. 2008. PMID: 18511197
-
[The role of mitogen-activated protein kinase cascades in inhibition of proliferation in human prostate carcinoma cells by raloxifene: an in vitro experiment].Zhonghua Yi Xue Za Zhi. 2008 Jan 22;88(4):271-5. Zhonghua Yi Xue Za Zhi. 2008. PMID: 18361842 Chinese.
-
Transforming growth factor-beta 1 increases bad phosphorylation and protects neurons against damage.J Neurosci. 2002 May 15;22(10):3898-909. doi: 10.1523/JNEUROSCI.22-10-03898.2002. J Neurosci. 2002. PMID: 12019309 Free PMC article.
-
Flavonoids protect neurons from oxidized low-density-lipoprotein-induced apoptosis involving c-Jun N-terminal kinase (JNK), c-Jun and caspase-3.Biochem J. 2001 Sep 15;358(Pt 3):547-57. doi: 10.1042/0264-6021:3580547. Biochem J. 2001. PMID: 11535118 Free PMC article.
Cited by
-
A Tale of Two: When Neural Stem Cells Encounter Hypoxia.Cell Mol Neurobiol. 2023 Jul;43(5):1799-1816. doi: 10.1007/s10571-022-01293-6. Epub 2022 Oct 29. Cell Mol Neurobiol. 2023. PMID: 36308642 Review.
-
Neuroprotective and Regenerative Effects of Growth Hormone (GH) in the Embryonic Chicken Cerebral Pallium Exposed to Hypoxic-Ischemic (HI) Injury.Int J Mol Sci. 2022 Aug 13;23(16):9054. doi: 10.3390/ijms23169054. Int J Mol Sci. 2022. PMID: 36012320 Free PMC article.
-
Glia-Derived Extracellular Vesicles: Role in Central Nervous System Communication in Health and Disease.Front Cell Dev Biol. 2021 Jan 25;8:623771. doi: 10.3389/fcell.2020.623771. eCollection 2020. Front Cell Dev Biol. 2021. PMID: 33569385 Free PMC article. Review.
-
Protopanaxadiol ginsenoside Rd protects against NMDA receptor-mediated excitotoxicity by attenuating calcineurin-regulated DAPK1 activity.Sci Rep. 2020 May 15;10(1):8078. doi: 10.1038/s41598-020-64738-2. Sci Rep. 2020. PMID: 32415270 Free PMC article.
-
Regulation of mitochondrial metabolism in murine skeletal muscle by the medium-chain fatty acid receptor Gpr84.FASEB J. 2019 Nov;33(11):12264-12276. doi: 10.1096/fj.201900234R. Epub 2019 Aug 15. FASEB J. 2019. PMID: 31415180 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous