Tags

Type your tag names separated by a space and hit enter

Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3'-kinase/protein kinase B signaling.
J Neurosci. 2000 Sep 15; 20(18):6962-7.JN

Abstract

The neurotrophin brain-derived neurotrophic factor (BDNF) serves as a survival, mitogenic, and differentiation factor in both the developing and adult CNS and PNS. In an attempt to identify the molecular mechanisms underlying BDNF neuroprotection, we studied activation of two potentially neuroprotective signal transduction pathways by BDNF in a CNS trauma model. Transection of the optic nerve (ON) in the adult rat induces secondary death of retinal ganglion cells (RGCs). Repeated intraocular injections of BDNF prevent the degeneration of RGCs 14 d after ON lesion most likely by inhibition of apoptosis. Here, we report that BDNF activates both protein kinase B (PKB) via a phosphatidyl-inositol-3'-kinase (PI-3-K)-dependent mechanism and the mitogen-activated protein kinases extracellular signal-regulated kinase 1 (ERK1) and ERK2. Furthermore, we provide evidence that BDNF suppresses cleavage and enzymatic activity of the neuronal cell death effector caspase-3. Distinct from our recent study in which inhibition of the PI-3-K/PKB pathway attenuated the survival-promoting action of insulin-like growth factor-I on axotomized RGCs (Kermer et al., 2000), it does not in the case of BDNF. Thus, we assume that BDNF does not depend on a single signal transduction pathway exerting its neuroprotective effects on lesioned CNS neurons.

Authors+Show Affiliations

Department of Neurology, University of Tübingen, 72076 Tübingen, Germany. nikolaj.kloecker@uni-tuebingen.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10995840

Citation

Klöcker, N, et al. "Brain-derived Neurotrophic Factor-mediated Neuroprotection of Adult Rat Retinal Ganglion Cells in Vivo Does Not Exclusively Depend On Phosphatidyl-inositol-3'-kinase/protein Kinase B Signaling." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 20, no. 18, 2000, pp. 6962-7.
Klöcker N, Kermer P, Weishaupt JH, et al. Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3'-kinase/protein kinase B signaling. J Neurosci. 2000;20(18):6962-7.
Klöcker, N., Kermer, P., Weishaupt, J. H., Labes, M., Ankerhold, R., & Bähr, M. (2000). Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3'-kinase/protein kinase B signaling. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 20(18), 6962-7.
Klöcker N, et al. Brain-derived Neurotrophic Factor-mediated Neuroprotection of Adult Rat Retinal Ganglion Cells in Vivo Does Not Exclusively Depend On Phosphatidyl-inositol-3'-kinase/protein Kinase B Signaling. J Neurosci. 2000 Sep 15;20(18):6962-7. PubMed PMID: 10995840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain-derived neurotrophic factor-mediated neuroprotection of adult rat retinal ganglion cells in vivo does not exclusively depend on phosphatidyl-inositol-3'-kinase/protein kinase B signaling. AU - Klöcker,N, AU - Kermer,P, AU - Weishaupt,J H, AU - Labes,M, AU - Ankerhold,R, AU - Bähr,M, PY - 2000/9/21/pubmed PY - 2000/10/21/medline PY - 2000/9/21/entrez SP - 6962 EP - 7 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 20 IS - 18 N2 - The neurotrophin brain-derived neurotrophic factor (BDNF) serves as a survival, mitogenic, and differentiation factor in both the developing and adult CNS and PNS. In an attempt to identify the molecular mechanisms underlying BDNF neuroprotection, we studied activation of two potentially neuroprotective signal transduction pathways by BDNF in a CNS trauma model. Transection of the optic nerve (ON) in the adult rat induces secondary death of retinal ganglion cells (RGCs). Repeated intraocular injections of BDNF prevent the degeneration of RGCs 14 d after ON lesion most likely by inhibition of apoptosis. Here, we report that BDNF activates both protein kinase B (PKB) via a phosphatidyl-inositol-3'-kinase (PI-3-K)-dependent mechanism and the mitogen-activated protein kinases extracellular signal-regulated kinase 1 (ERK1) and ERK2. Furthermore, we provide evidence that BDNF suppresses cleavage and enzymatic activity of the neuronal cell death effector caspase-3. Distinct from our recent study in which inhibition of the PI-3-K/PKB pathway attenuated the survival-promoting action of insulin-like growth factor-I on axotomized RGCs (Kermer et al., 2000), it does not in the case of BDNF. Thus, we assume that BDNF does not depend on a single signal transduction pathway exerting its neuroprotective effects on lesioned CNS neurons. SN - 0270-6474 UR - https://www.unboundmedicine.com/medline/citation/10995840/Brain_derived_neurotrophic_factor_mediated_neuroprotection_of_adult_rat_retinal_ganglion_cells_in_vivo_does_not_exclusively_depend_on_phosphatidyl_inositol_3'_kinase/protein_kinase_B_signaling_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=10995840 DB - PRIME DP - Unbound Medicine ER -