Stimulation of astrocyte-enriched culture with arachidonic acid increases proenkephalin mRNA: involvement of proto-oncoprotein and mitogen activated protein kinases.
In astrocyte-enriched cultures, arachidonic acid (AA, 100 microM) significantly increased the proenkephalin (proENK) mRNA level (4. 9-fold at 8 h). In addition, AA also increased several AP-1 proteins, such as c-Fos, Fra-1, Fra-2, JunB, JunD, and c-Jun, or AP-1 and ENKCRE-2 DNA-binding activity. As well as AP-1 proteins and their DNA-binding activities, proENK mRNA level induced by AA was reduced by the pretreatment with 15 microM of cycloheximide (CHX; 1.6-fold). AA-dependent increase of proENK mRNA is not mediated by cyclooxygenase- or lipoxygenase-dependent metabolites, or free radicals, because the AA-induced increase of proENK mRNA levels was not affected by indomethacin (10 microM), nordihydroguaiaretic acid (10 microM), or N-acetylcysteine. However, as well as proto-oncoprotein levels, such as Fra-1, Fra-2, c-Jun, JunB, but not JunD, AA-induced increase of proENK mRNA was significantly reduced by the pretreatment with 10 microM of PD98059 (1.3-fold) or 10 microM of SB203580 (1.8-fold). These results strongly suggest that AA rather than one of its metabolites is involved in the increase of proENK mRNA. In addition, the activation of both the p38 and ERK pathways appears to be involved in the AA-induced increase of proENK mRNA via activating the expression of proto-oncoprotein, such as Fra-1, Fra-2, c-Jun, and JunB.
Won
J S
JS
Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, 1 Okchun-Dong, Chunchon, Kangwon-Do, South Korea.
Kim
Y H
YH
Song
D K
DK
Huh
S O
SO
Lee
J K
JK
Suh
H W
HW
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D004745:Enkephalins / Q000235:genetics*; D004789:Enzyme Activation; D051921:Fos-Related Antigen-2; D005786:Gene Expression Regulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D009637:Masoprocol / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D048051:p38 Mitogen-Activated Protein Kinases; D000099169:Fos-Related Antigen 1
D000111:Acetylcysteine; D016718:Arachidonic Acid; D004268:DNA-Binding Proteins; D004745:Enkephalins; D051921:Fos-Related Antigen-2; D007213:Indomethacin; D009637:Masoprocol; D020928:Mitogen-Activated Protein Kinases; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; D000099169:Fos-Related Antigen 1; C497874:Fosl2 protein, rat; C029992:proenkephalin