PMID- 18445478 OWN - NLM STAT- MEDLINE DCOM- 20080703 LR - 20211203 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 371 IP - 3 DP - 2008 Jul 4 TI - 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. PG - 495-500 LID - 10.1016/j.bbrc.2008.04.102 [doi] AB - 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. FAU - Yoon, Hana AU - Yoon H AD - Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. FAU - Oh, Young Taek AU - Oh YT FAU - Lee, Jung Yeon AU - Lee JY FAU - Choi, Ji Hyun AU - Choi JH FAU - Lee, Ju Hie AU - Lee JH FAU - Baik, Hyung Hwan AU - Baik HH FAU - Kim, Sung Soo AU - Kim SS FAU - Choe, Wonchae AU - Choe W FAU - Yoon, Kyung-Sik AU - Yoon KS FAU - Ha, Joohun AU - Ha J FAU - Kang, Insug AU - Kang I LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080428 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Multienzyme Complexes) RN - 0 (NF-kappa B) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Kainic Acid) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - SIV03811UC (Kainic Acid) RN - SY7Q814VUP (Calcium) SB - IM MH - AMP-Activated Protein Kinases MH - Animals MH - Brain-Derived Neurotrophic Factor/genetics/*metabolism MH - Calcium/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism MH - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism MH - Cell Line, Tumor MH - Enzyme Activation MH - Glioma MH - Kainic Acid/*pharmacology MH - Multienzyme Complexes/antagonists & inhibitors/*metabolism MH - NF-kappa B/*metabolism MH - Phosphorylation MH - Protein Serine-Threonine Kinases/antagonists & inhibitors/*metabolism MH - RNA, Messenger/metabolism MH - Rats MH - Receptors, Kainic Acid/agonists/metabolism MH - Transcriptional Activation EDAT- 2008/05/01 09:00 MHDA- 2008/07/04 09:00 CRDT- 2008/05/01 09:00 PHST- 2008/03/27 00:00 [received] PHST- 2008/04/19 00:00 [accepted] PHST- 2008/05/01 09:00 [pubmed] PHST- 2008/07/04 09:00 [medline] PHST- 2008/05/01 09:00 [entrez] AID - S0006-291X(08)00789-4 [pii] AID - 10.1016/j.bbrc.2008.04.102 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2008 Jul 4;371(3):495-500. doi: 10.1016/j.bbrc.2008.04.102. Epub 2008 Apr 28.