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.
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.
Yoon
Hana
H
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
Oh
Young Taek
YT
Lee
Jung Yeon
JY
Choi
Ji Hyun
JH
Lee
Ju Hie
JH
Baik
Hyung Hwan
HH
Kim
Sung Soo
SS
Choe
Wonchae
W
Yoon
Kyung-Sik
KS
Ha
Joohun
J
Kang
Insug
I
D055372:AMP-Activated Protein Kinases; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005910:Glioma; D007608:Kainic Acid / Q000494:pharmacology*; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018092:Kainic Acid Receptors / Q000819:agonists / Q000378:metabolism; D015533:Transcriptional Activation
D055372:AMP-Activated Protein Kinases; D019208:Brain-Derived Neurotrophic Factor; D002118:Calcium; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D007608:Kainic Acid; D009097:Multienzyme Complexes; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018092:Kainic Acid Receptors