Brain‐Derived Neurotrophic Factor Enhances Bcl‐xL Expression Through Protein Kinase Casein Kinase 2‐Activated and Nuclear Factor Kappa B‐Mediated Pathway in Rat Hippocampus
- 27 January 2011
- journal article
- Published by Wiley in Brain Pathology
- Vol. 21 (2), 150-162
- https://doi.org/10.1111/j.1750-3639.2010.00431.x
Abstract
Brain‐derived neurotrophic factor (BDNF) was shown to produce its neuroprotective effect through extracellular signal‐regulated kinase 1/2 (ERK1/2) and phosphatidylinositol‐3 kinase (PI3‐K) signaling. But whether other pathways also mediate the neuroprotective effect of BDNF is less known. In this study, we found that direct administration of BDNF to rat hippocampal CA1 area dose‐dependently increased the mRNA and protein levels of Bcl‐xL. BDNF also increased protein kinase casein kinase II (CK2) activity and NF‐κB phosphorylation at Ser529 dose‐dependently. Further, transfection of the wild‐type CK2α DNA to CA1 neurons increased nuclear factor kappa B (NF‐κB) phosphorylation and Bcl‐xL mRNA expression, whereas transfection of CK2α156A, the catalytically inactive mutant of CK2α, decreased these measures. Moreover, transfection of CK2α small interfering RNA (siRNA) blocked the enhancing effect of BDNF on NF‐κB phosphorylation and Bcl‐xL expression. These results were further confirmed by treatment of 4,5,6,7‐tetrabromobenzotriazole (TBB), a specific CK2 inhibitor. Transfection of NF‐κBS529A, the dominant negative mutant of NF‐κB, prevented the enhancing effect of BDNF on Bcl‐xL expression. More importantly, BDNF activation of CK2 is not affected by co‐administration of the ERK1/2 inhibitor, PD98059, and the PI3‐K inhibitor, LY294002. These results demonstrate a novel BDNF signaling pathway and provide an alternative therapeutic strategy for the protective effect of BDNF on hippocampal neurons in vivo.Keywords
This publication has 45 references indexed in Scilit:
- Casein kinase II contributes to the synergistic effects of BMP7 and BDNF on Smad 1/5/8 phosphorylation in septal neurons under hypoglycemic stressJournal of Neurochemistry, 2009
- Selective Erasure of a Fear MemoryScience, 2009
- Protein kinase CK2 – A key suppressor of apoptosisAdvances in Enzyme Regulation, 2008
- The BCL-2 protein family: opposing activities that mediate cell deathNature Reviews Molecular Cell Biology, 2008
- Antiapoptotic Effects of Progastrin on Pancreatic Cancer Cells Are Mediated by Sustained Activation of Nuclear Factor-κBCancer Research, 2007
- Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memoriesMolecular Psychiatry, 2007
- CK2 Is a Component of the KSR1 Scaffold Complex that Contributes to Raf Kinase ActivationCurrent Biology, 2007
- Platelet-Activating Factor Induces Up-regulation of Antiapoptotic Factors in a Melanoma Cell Line through Nuclear Factor-κB ActivationCancer Research, 2006
- Protein kinase CK2 phosphorylates and upregulates Akt/PKBCell Death & Differentiation, 2005
- Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein stabilization and apoptosis of immortalized hepatocytesHepatology, 2003