We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Canonical Nuclear Factor-κB Pathway Regulates Cell Survival in a Developmental Model of Spinal Cord Motoneurons.
- Authors
incheva, Stefka; Garcera, Ana; Gou-Fabregas, Myriam; Encinas, Mario; Dolcet, Xavier; Soler, Rosa M.
- Abstract
In vivo and in vitro motoneuron survival depends on the support of neurotrophic factors. These factors activate signaling pathways related to cell survival or inactivate proteins involved in neuronal death. In the present work, we analyzed the involvement of the nuclear factor-B (NF-κB) pathway in mediating mouse spinal cord motoneuron survival promoted by neurotrophic factors. This pathway comprises ubiquitously expressed transcription factors that could be activated by two different routes: the canonical pathway, associated with IKKβ/IKKβ kinase phosphorylation and nuclear translocation RelA (p65)/p50 transcription factors; and the noncanonical pathway, related to IKKβ kinase homodimer phosphorylation and RelB/p52 transcription factor activation. In our system, we show that neurotrophic factors treatment induced IKKβ and IKKβ phosphorylation and RelA nuclear translocation, suggesting NF-κB pathway activation. Protein levels of different members of the canonical or noncanonical pathways were reduced in a primary culture of isolated embryonic motoneurons using an interferenceRNAapproach. Even in the presence of neurotrophic factors, selective reduction of IKKβ, IKKβ, or RelA proteins induced cell death. In contrast, RelB protein reduction did not have a negative effect on motoneuron survival. Together these results demonstrated that the canonical NF-κB pathway mediates motoneuron survival induced by neurotrophic factors, and the noncanonical pathway is not related to this survival effect. Canonical NF-κB blockade induced an increase of Bim protein level and apoptotic cell death. Bcl-xL overexpression
- Subjects
DEVELOPMENTAL biology; MOTOR neurons; CELL death; NF-kappa B; PHOSPHORYLATION; IMMUNOGLOBULINS
- Publication
Journal of Neuroscience, 2011, Vol 31, Issue 17, p6493
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0206-11.2011