The bradykinin B2 receptor mediates hypoxia/reoxygenation induced neuronal cell apoptosis through the ERK1/2 pathway

Neurosci Lett. 2009 Jan 23;450(1):40-4. doi: 10.1016/j.neulet.2008.10.110. Epub 2008 Nov 14.

Abstract

The bradykinin B2 receptor (B2R) mediates many physiological processes such as hypotension, inflammation and blood-vessel permeability. Hypoxia/reoxygenation (H/R) induces neuronal cell apoptosis. It was found that B2R expression was enhanced in primary cultured cortical neurons after H/R treatment. Addition of bradykinin (BK) alleviated the neuronal damage from H/R. This protective effect of BK was inhibited by the B2R antagonist, HOE140, and the ERK1/2 antagonist, PD98059. The phosphorylation of ERK1/2 was increased under H/R, and the addition of BK enhanced this effect. These results indicate that B2R plays an important role in protecting neurons from damage induced by H/R and this effect may function through the ERK1/2 pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Bradykinin / therapeutic use
  • Bradykinin B2 Receptor Antagonists
  • Cell Hypoxia*
  • Cells, Cultured
  • Culture Media
  • Flavonoids / pharmacology
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Oxygen / metabolism*
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Bradykinin B2 / metabolism*
  • Reperfusion Injury / physiopathology

Substances

  • Bradykinin B2 Receptor Antagonists
  • Culture Media
  • Flavonoids
  • Protein Kinase Inhibitors
  • Receptor, Bradykinin B2
  • icatibant
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Oxygen
  • Bradykinin
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one