Annexin-1 Mediates Microglial Activation and Migration via the CK2 Pathway during Oxygen-Glucose Deprivation/Reperfusion

Int J Mol Sci. 2016 Oct 22;17(10):1770. doi: 10.3390/ijms17101770.


Annexin-1 (ANXA1) has shown neuroprotective effects and microglia play significant roles during central nervous system injury, yet the underlying mechanisms remain unclear. This study sought to determine whether ANXA1 regulates microglial response to oxygen-glucose deprivation/reperfusion (OGD/R) treatment and to clarify the downstream molecular mechanism. In rat hippocampal slices, OGD/R treatment enhanced the ANXA1 expression in neuron, the formyl peptide receptor (FPRs) expression in microglia, and the microglial activation in the CA1 region (cornu ammonis 1). These effects were reversed by the FPRs antagonist Boc1. The cell membrane currents amplitude of BV-2 microglia (the microglial like cell-line) was increased when treated with Ac2-26, the N-terminal peptide of ANXA1. Ac2-26 treatment enhanced BV-2 microglial migration whereas Boc1 treatment inhibited the migration. In BV-2 microglia, both the expression of the CK2 target phosphorylated α-E-catenin and the binding of casein kinase II (CK2) with α-E-catenin were elevated by Ac2-26, these effects were counteracted by the CK2 inhibitor TBB and small interfering (si) RNA directed against transcripts of CK2 and FPRs. Moreover, both TBB and siRNA-mediated inhibition of CK2 blocked Ac2-26-mediated BV-2 microglia migration. Our findings indicate that ANXA1 promotes microglial activation and migration during OGD/R via FPRs, and CK2 target α-E-catenin phosphorylation is involved in this process.

Keywords: ANXA1; CK2; OGD/R; activation; microglia; migration.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism*
  • Annexin A1 / pharmacology
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Cell Hypoxia
  • Cell Line
  • Cell Movement / drug effects
  • Female
  • Gene Expression Regulation
  • Glucose / deficiency*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • Male
  • Microglia / cytology
  • Microglia / drug effects
  • Microglia / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism
  • Oligopeptides / pharmacology
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Phosphorylation / drug effects
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Formyl Peptide / antagonists & inhibitors
  • Receptors, Formyl Peptide / genetics
  • Receptors, Formyl Peptide / metabolism
  • Tissue Culture Techniques
  • Triazoles / pharmacology
  • alpha Catenin / antagonists & inhibitors
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*


  • 4,5,6,7-tetrabromobenzotriazole
  • Annexin A1
  • Oligopeptides
  • Peptides
  • RNA, Small Interfering
  • Receptors, Formyl Peptide
  • Triazoles
  • alpha Catenin
  • annexin A1 peptide (2-26)
  • t-butyloxycarbonyl-methionyl-leucyl-phenylalanine
  • Casein Kinase II
  • Glucose