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

Hana Yoon; Young Taek Oh; Jung Yeon Lee; Ji Hyun Choi; Ju Hie Lee; Hyung Hwan Baik; Sung Soo Kim; Wonchae Choe; Kyung-Sik Yoon; Joohun Ha; Insug Kang

doi:10.1016/j.bbrc.2008.04.102

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.

Authors

Hana Yoon¹, Young Taek Oh, Jung Yeon Lee, Ji Hyun Choi, Ju Hie Lee, Hyung Hwan Baik, Sung Soo Kim, Wonchae Choe, Kyung-Sik Yoon, Joohun Ha, Insug Kang

Affiliation

¹ Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.

PMID: 18445478
DOI: 10.1016/j.bbrc.2008.04.102

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