4.6 Article

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

Journal

BRAIN PATHOLOGY
Volume 21, Issue 2, Pages 150-162

Publisher

WILEY
DOI: 10.1111/j.1750-3639.2010.00431.x

Keywords

Bcl-xL; brain-derived neurotrophic factor; casein kinase 2; hippocampus; neuroprotection; NF-kappa B

Funding

  1. National Science Council of Taiwan [NSC 96-2320-B-320-012-MY2]
  2. Institute of Biomedical Sciences (IBMS), Academia Sinica in Taiwan

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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-kappa B phosphorylation at Ser529 dose-dependently. Further, transfection of the wild-type CK2 alpha DNA to CA1 neurons increased nuclear factor kappa B (NF-kappa B) phosphorylation and Bcl-xL mRNA expression, whereas transfection of CK2 alpha 156A, the catalytically inactive mutant of CK2 alpha, decreased these measures. Moreover, transfection of CK2 alpha small interfering RNA (siRNA) blocked the enhancing effect of BDNF on NF-kappa B 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-kappa BS529A, the dominant negative mutant of NF-kappa B, 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.

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