ERK1/2 activity is critical for the outcome of ischemic stroke
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-283991
- Ischemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2\(^{wt}\)) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brainIschemic disorders are the leading cause of death worldwide. The extracellular signal-regulated kinases 1 and 2 (ERK1/2) are thought to affect the outcome of ischemic stroke. However, it is under debate whether activation or inhibition of ERK1/2 is beneficial. In this study, we report that the ubiquitous overexpression of wild-type ERK2 in mice (ERK2\(^{wt}\)) is detrimental after transient occlusion of the middle cerebral artery (tMCAO), as it led to a massive increase in infarct volume and neurological deficits by increasing blood–brain barrier (BBB) leakiness, inflammation, and the number of apoptotic neurons. To compare ERK1/2 activation and inhibition side-by-side, we also used mice with ubiquitous overexpression of the Raf-kinase inhibitor protein (RKIP\(^{wt}\)) and its phosphorylation-deficient mutant RKIP\(^{S153A}\), known inhibitors of the ERK1/2 signaling cascade. RKIP\(^{wt}\) and RKIP\(^{S153A}\) attenuated ischemia-induced damages, in particular via anti-inflammatory signaling. Taken together, our data suggest that stimulation of the Raf/MEK/ERK1/2-cascade is severely detrimental and its inhibition is rather protective. Thus, a tight control of the ERK1/2 signaling is essential for the outcome in response to ischemic stroke.…
Autor(en): | Constanze Schanbacher, Michael Bieber, Yvonne Reinders, Deya Cherpokova, Christina Teichert, Bernhard Nieswandt, Albert Sickmann, Christoph Kleinschnitz, Friederike Langhauser, Kristina Lorenz |
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URN: | urn:nbn:de:bvb:20-opus-283991 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Pharmakologie und Toxikologie |
Medizinische Fakultät / Neurologische Klinik und Poliklinik | |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Medizinische Fakultät / Institut für Experimentelle Biomedizin | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 23 |
Heft / Ausgabe: | 2 |
Aufsatznummer: | 706 |
Originalveröffentlichung / Quelle: | International Journal of Molecular Sciences (2022) 23:2, 706. https://doi.org/10.3390/ijms23020706 |
DOI: | https://doi.org/10.3390/ijms23020706 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | ERK1/2; RKIP; ischemic stroke; tMCAO |
Datum der Freischaltung: | 14.07.2023 |
Datum der Erstveröffentlichung: | 09.01.2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |