title: Cycloheximide increases proenkephalin and tyrosine hydroxylase gene expression in rat adrenal medulla.
abstract: The effect of cycloheximide (CHX; 5 mg/kg) on proenkephalin (proENK) and tyrosine hydroxylase (TH) mRNA expression in rat central and peripheral nervous systems was studied. CHX increased proENK and TH mRNA levels in the adrenal gland, but not in hippocampus, striatum, midbrain, brainstem, pituitary, and hypothalamus. The pretreatment with actinomycin D (0.5 mg/kg) significantly decreased CHX-induced proENK and TH mRNA expression, suggesting that the CHX-dependent increase of these mRNA levels may be caused by the increase of transcriptional activity rather than RNA stabilization. To investigate the factors involved in CHX-induced proENK and TH mRNA expression, the effect of CHX on activator protein-1 (AP-1), cAMP response element (CRE) binding protein (CREB), and glucocorticoid response element (GRE) was tested. In AP-1, the basal expression of Fra-2 and c-Jun proteins and AP-1 DNA binding activity in the adrenal medulla was higher than other tissues tested, but CHX reduced these protein levels and AP-1 DNA binding activity. In CREB, CHX time dependently increased the level of phospho-CREB without altering total CRE level and CRE DNA binding activity. Furthermore, phospho-CREB actively participated in CRE DNA binding activity. In GRE, although CHX increased plasma and adrenal corticosterone level, RU486 (10 mg/kg) reduced CHX-induced proENK, but not TH, mRNA level in a partial manner. These results suggest that the basal expression of proENK and TH mRNA transcription in the adrenal gland seems to be tonically inhibited by de novo protein synthesis. In addition, CHX-dependent increase of proENK and TH mRNA expression in the adrenal medulla is well correlated with phospho-CREB level, but not AP-1. Finally, glucocorticoid seems to be involved at least partially in CHX-dependent proENK, but not TH, mRNA expression in the adrenal medulla.
authors.affiliation: Department of Pharmacology and Institute of Natural Medicine, College of Medicine, Hallym University, Chunchon, Kangwon-Do, Republic of Korea.
authors.forename: J S
authors.initials: JS
authors.lastname: Won
authors.forename: J K
authors.initials: JK
authors.lastname: Lee
authors.forename: D K
authors.initials: DK
authors.lastname: Song
authors.forename: S O
authors.initials: SO
authors.lastname: Huh
authors.forename: J S
authors.initials: JS
authors.lastname: Jung
authors.forename: Y H
authors.initials: YH
authors.lastname: Kim
authors.forename: M R
authors.initials: MR
authors.lastname: Choi
authors.forename: H W
authors.initials: HW
authors.lastname: Suh
mesh_terms: D051698:Activating Transcription Factor 2; D000313:Adrenal Medulla / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000493:pharmacokinetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism; D010766:Phosphorylation; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004745:Enkephalins; D011498:Protein Precursors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; C029992:proenkephalin; D015735:Mifepristone; D004247:DNA; D003513:Cycloheximide; D014446:Tyrosine 3-Monooxygenase; D020928:Mitogen-Activated Protein Kinases; D003345:Corticosterone