Activation of AMP-activated protein kinase by kainic acid mediates brain-derived neurotrophic factor expression through a NF-kappaB dependent mechanism in C6 glioma cells

Biochem Biophys Res Commun. 2008 Jul 4;371(3):495-500. doi: 10.1016/j.bbrc.2008.04.102. Epub 2008 Apr 28.

Abstract

AMP-activated protein kinase (AMPK) is a key regulator of energy homeostasis. Kainic acid (KA), a prototype excitotoxin is known to induce brain-derived neurotrophic factor (BDNF) in brain. In this study, we examined the role of AMPK in KA-induced BDNF expression in C6 glioma cells. We showed that KA and KA receptor agonist induced activation of AMPK and KA-induced AMPK activation was blocked by inhibition of Ca(2+)/calmodulin-dependent protein kinase kinase (CaMKK) beta. We then showed that inhibition of AMPK by compound C, a selective inhibitor of AMPK, or small interfering RNA of AMPKalpha1 blocked KA-induced BDNF mRNA and protein expression. Inhibition of AMPK blocked KA-induced phosphorylation of CaMKII and I kappaB kinase (IKK) in C6 cells. Finally, we showed that inhibition of AMPK reduced DNA binding and transcriptional activation of nuclear factor-kappaB (NF-kappaB) in KA-treated cells. These results suggest that AMPK mediates KA-induced BDNF expression by regulating NF-kappaB activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cell Line, Tumor
  • Enzyme Activation
  • Glioma
  • Kainic Acid / pharmacology*
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism*
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Kainic Acid / agonists
  • Receptors, Kainic Acid / metabolism
  • Transcriptional Activation

Substances

  • Brain-Derived Neurotrophic Factor
  • Multienzyme Complexes
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Kainic Acid
  • Protein-Serine-Threonine Kinases
  • Calcium-Calmodulin-Dependent Protein Kinase Kinase
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • AMP-Activated Protein Kinases
  • Kainic Acid
  • Calcium