Document Detail


Stimulation of astrocyte-enriched culture with C2 ceramide increases proenkephalin mRNA: involvement of cAMP-response element binding protein and mitogen activated protein kinases.
MedLine Citation:
PMID:  11382404     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In rat astrocyte-enriched culture, C2 ceramide dose- and time-dependently increased proenkephalin (proENK) mRNA; the significant increase began at 6 h after 30 microM C2 ceramide treatment (about 13-fold) and at 12 h after treatment (about 21-fold). In addition, C2 ceramide also increased AP-1 proteins, such as Fra-1, c-Jun, JunB and JunD, and phosphorylation of CREB. The blocking of protein synthesis by cycloheximide (CHX) evokes a further increase of C2 ceramide-induced proENK mRNA and phospho-CREB level, while C2 ceramide-induced increases of AP-1 protein levels were reduced by CHX. The C2 ceramide-induced proENK mRNA expression was not changed significantly by the pretreatment with H89 (a PKA inhibitor), KN62 (a calcium/calmodulin-dependent protein kinase II inhibitor), and PD98059 (an ERK pathway inhibitor). However, calphostin C (a PKC inhibitor) and or SB203580 (a p38 inhibitor) partially but significantly reduced C2 ceramide-induced proENK mRNA expression as well as phospho-CREB level. These results suggest that, in the rat astrocyte-enriched culture, C2 ceramide increases proENK mRNA expression via phosphorylation of CREB rather than the increases of AP-1 protein levels. Additionally, the activations of PKC and p38, but not PKA, calcium/calmodulin-dependent protein kinase II, and ERK, by C2 ceramide play important regulatory roles in C2 ceramide-induced proENK mRNA expression via activating the CREB.
Authors:
J S Won; M R Choi; H W Suh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Brain research     Volume:  903     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-05-30     Completed Date:  2001-08-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  207-15     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do 200-702, South Korea.
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives,  pharmacology
Animals
Astrocytes / cytology,  enzymology*
Cells, Cultured
Cyclic AMP Response Element-Binding Protein / metabolism*
Cycloheximide / pharmacology
Enkephalins / genetics*
Enzyme Inhibitors / pharmacology
Flavonoids / pharmacology
Gene Expression / drug effects
Imidazoles / pharmacology
Isoquinolines / pharmacology
Mitogen-Activated Protein Kinases / metabolism*
Naphthalenes / pharmacology
Phosphorylation
Protein Precursors / genetics*
Protein Synthesis Inhibitors / pharmacology
Pyridines / pharmacology
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Sphingosine / analogs & derivatives,  pharmacology*
Stimulation, Chemical
Sulfonamides*
Transcription Factor AP-1 / metabolism
Chemical
Reg. No./Substance:
0/Cyclic AMP Response Element-Binding Protein; 0/Enkephalins; 0/Enzyme Inhibitors; 0/Flavonoids; 0/Imidazoles; 0/Isoquinolines; 0/N-acetylsphingosine; 0/Naphthalenes; 0/PD 98059; 0/Protein Precursors; 0/Protein Synthesis Inhibitors; 0/Pyridines; 0/RNA, Messenger; 0/SB 203580; 0/Sulfonamides; 0/Transcription Factor AP-1; 0/proenkephalin; 121263-19-2/calphostin C; 123-78-4/Sphingosine; 127191-97-3/KN 62; 127243-85-0/H 89; 66-81-9/Cycloheximide; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 2.7.11.24/Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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