title: The role of inducible repressor proteins in the adrenergic induction of arylalkylamine-N-acetyltransferase and mitogen-activated protein kinase phosphatase-1 in rat pinealocytes.
abstract: In this study, we investigated the role of two inducible repressor proteins, inducible cAMP early repressor (ICER) and Fos-related antigen 2 (Fra-2) in the adrenergic induction of MAPK phosphatase-1 (MKP-1) as compared with their roles in the induction of arylalkylamine-N-acetyltransferase (AA-NAT) in rat pinealocytes. Treatment of pinealocytes with norepinephrine (NE) caused an increase in the mRNA and protein levels of MKP-1 and AA-NAT, as well as in the AA-NAT activity and melatonin production. NE stimulation also caused a simultaneous increase in the mRNA and protein levels of ICER and Fra-2. Transient knockdown of icer using adenovirus expressing small interfering RNA (siRNA) abolished the NE induction of icer expression but had little effect on the NE induction of mkp-1 or aa-nat expression. In contrast, pretreatment with adenovirus overexpressing icer was effective in reducing the NE induction of mkp-1 and aa-nat. The inhibitory effect of overexpressing icer was reversed by cotreatment with siRNA against icer. siRNA against fra-2 also abolished the NE-stimulated expression of fra-2 but had little effect on the NE induction of mkp-1 and aa-nat expression. Proteasomal inhibition, which reduced the NE-stimulated induction of aa-nat, caused a reduction of ICER and Fra-2. Together, these results indicate that whereas overexpression of ICER can suppress the NE induction of aa-nat and mkp-1, the amount of the repressors, ICER and Fra-2, present during NE induction appears insufficient to exert a significant effect in controlling the expression of these genes.
authors.affiliation: Department of Medicine, 7-26 Medical Sciences Building, Edmonton, Alberta, Canada. anho@ualberta.ca
authors.forename: A K
authors.initials: AK
authors.lastname: Ho
authors.forename: D L
authors.initials: DL
authors.lastname: Terriff
authors.forename: D M
authors.initials: DM
authors.lastname: Price
authors.forename: M T
authors.initials: MT
authors.lastname: Wloka
authors.forename: C L
authors.initials: CL
authors.lastname: Chik
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000096:biosynthesis*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D051786:Cyclic AMP Response Element Modulator / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D054638:Dual Specificity Phosphatase 1; D051921:Fos-Related Antigen-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018014:Gene Transfer Techniques; D017874:Immediate-Early Proteins / Q000096:biosynthesis*; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010749:Phosphoprotein Phosphatases / Q000096:biosynthesis*; D010870:Pineal Gland / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D061988:Proteasome Inhibitors; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000096:biosynthesis*; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000316:Adrenergic alpha-Agonists; D018797:Cell Cycle Proteins; C497412:Crem protein, rat; D051921:Fos-Related Antigen-2; D017874:Immediate-Early Proteins; D007783:Lactones; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D051786:Cyclic AMP Response Element Modulator; C098869:clasto-lactacystin beta-lactone; D047068:Arylalkylamine N-Acetyltransferase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases; D009638:Norepinephrine