Interleukin-1 beta protects neurons via the interleukin-1 (IL-1) receptor-mediated Akt pathway and by IL-1 receptor-independent decrease of transmembrane currents in vivo
2003 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Interleukin-1 beta protects neurons via the interleukin-1 (IL-1) receptor-mediated Akt pathway and by IL-1 receptor-independent decrease of transmembrane currents in vivo
Diem, R. ; Hobom, M.; Grotsch, P.; Krämer, B. & Bähr, M. (2003)
Molecular and Cellular Neuroscience, 22(4) pp. 487-500. DOI: https://doi.org/10.1016/S1044-7431(02)00042-8
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- Authors
- Diem, Ricarda ; Hobom, M.; Grotsch, P.; Krämer, Bernd; Bähr, Mathias
- Abstract
- Recently. we have demonstrated that tumor necrosis factor-alpha (TNF-alpha) rescues retinal ganglion cells (RGCs) from retrograde cell death in vivo after axotomy of the optic nerve. The mechanism of RGC rescue was dependent on TNF-receptor I-mediated potassium current reduction and consecutive activation of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Here, we present evidence that interleukin-1beta (IL-1beta) also promotes RGC survival, but shows distinct differences with respect to its neuroprotective mechanisms. Using whole-cell and outside-out patch-clamp techniques, we observed that IL-1beta decreased both inward sodium current amplitudes and outward potassium current amplitudes. Counteracting these effects by sodium or potassium channel opening inhibited the survival-promoting effects of this cytokine. IL-1beta-induced current reduction could not be abolished by the interleukin-1 receptor antagonist, indicating that the electrophysiological effects of IL-1beta are independent of interleukin-1 receptor I (IL-1RI) activation. Western blot analysis revealed an IL-1beta-induced IL-1RI-dependent Upregulation of phospho-Akt. Antagonism of the survival-promoting effects of IL-1beta by PI3-K inhibition revealed the functional relevance of the PI3-K/Akt pathway in IL-1beta-induced signal transduction in vivo. (C) 2003 Elsevier Science (USA). All rights reserved.
- Issue Date
- 2003
- Publisher
- Academic Press Inc Elsevier Science
- Journal
- Molecular and Cellular Neuroscience
- ISSN
- 1044-7431