Casein kinase II contributes to the synergistic effects of BMP7 and BDNF on Smad 1/5/8 phosphorylation in septal neurons under hypoglycemic stress

Florence Chaverneff, John Barrett

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The combination of bone morphogenetic protein 7 (BMP7) and neurotrophins (e.g. brain-derived neurotrophic factor, BDNF) protects septal neurons during hypoglycemic stress. We investigated the signaling mechanisms underlying this synergistic protection. BMP7 (5 nM) increased phosphorylation and nuclear translocation of BMP-responsive Smads 1/5/8 within 30 min in cultures of rat embryonic septal neurons. BDNF (100 ng/mL) enhanced the BMP7-induced increase in phospho-Smad levels in both nucleus and cytoplasm; this effect was more pronounced after a hypoglycemic stress. BDNF increased both Akt and Erk phosphorylation, but pharmacological blockade of these kinase pathways (with wortmannin and U0126, respectively) did not reduce the Smad phosphorylation produced by the BMP7 + BDNF combination. Inhibitors of casein kinase II (CK2) activity reduced the (BMP7 + BDNF)-induced Smad phosphorylation, and this trophic factor combination increased CK2 activity in hypoglycemic cultures. These findings suggest that BDNF can increase BMP-dependent Smad phosphorylation via a mechanism requiring CK2.

Original languageEnglish (US)
Pages (from-to)733-743
Number of pages11
JournalJournal of neurochemistry
Volume109
Issue number3
DOIs
StatePublished - May 1 2009

Keywords

  • Basal forebrain
  • Bone morphogenetic protein 7
  • Brain-derived neurotrophic growth factor
  • Casein kinase II
  • Hypoglycemia
  • Smad 1/5/8

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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