title: Possible roles of JNK pathway in the regulation of hippocampal proenkephalin and immediate early gene expression induced by kainic acid.
abstract: Mitogen-activated protein kinases (MAPKs) may play crucial roles in the kainic acid (KA)-evoked excitotoxic effect and the regulation of transcription factors (e.g. c-Fos and c-Jun) in hippocampus, but their exact role in the regulation of KA-induced opioid peptides expression has not been well characterized in vivo. Therefore, we examined possible involvement of the phosphorylated form of JNK, as well as CREB, in the regulation of KA-induced proenkephalin and immediate early genes (IEGs) expression in the rat hippocampus. KA increased proenkephalin mRNA expression in rat hippocampus, which was decreased by pre-administration with cycloheximide (CHX, a protein synthesis inhibitor). KA alone increased c-fos as well as c-jun mRNA levels. CHX further enhanced KA-induced c-fos and c-jun mRNA levels. Additionally, KA increased the phosphorylation of JNK, especially JNK1, which was attenuated by CHX. CHX decreased KA-induced c-Fos protein expression. Interestingly, CHX itself increased the phosphorylation of CREB, which was abolished by KA administration. Our results suggest that the phosphorylation of JNK is involved in the up-regulation of the proenkephalin gene expression via c-Fos and c-Jun that is induced by KA in rat hippocampus. However, the phosphorylation of CREB is not associated with the up-regulation of the proenkephalin mRNA level induced by KA in the rat hippocampus.
authors.affiliation: Department of Pharmacology, Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Korea.
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: S S
authors.initials: SS
authors.lastname: Choi
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: J S
authors.initials: JS
authors.lastname: Won
authors.forename: M R
authors.initials: MR
authors.lastname: Choi
authors.forename: H W
authors.initials: HW
authors.lastname: Suh
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology*; D017781:Genes, Immediate-Early; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D015151:Immunoblotting; D007608:Kainic Acid / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004745:Enkephalins; D018690:Excitatory Amino Acid Agonists; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C029992:proenkephalin; D003513:Cycloheximide; D048055:Mitogen-Activated Protein Kinase 8; D020928:Mitogen-Activated Protein Kinases; D007608:Kainic Acid