title: Regulation of the S100B gene by alpha 1-adrenergic stimulation in cardiac myocytes.
abstract: We previously reported that S100B, a 20-kDa Ca(2+)-binding homodimer, inhibited the postinfarct myocardial hypertrophic response mediated by alpha(1)-adrenergic stimulation through the protein kinase C (PKC) signaling pathway. In the present study, we examined whether the same pathway induced the S100B gene, supporting the hypothesis that S100B is a feedback negative regulator of this pathway. We transfected cultured neonatal rat cardiac myocytes with a luciferase reporter gene driven by the maximal human S100B promoter and progressively shorter segments of this promoter sequentially deleted from the 5' end. We identified a basic promoter essential for transcription spanning 162 bp upstream of the transcription initiation site and positive (at -782/-162 and -6,689/-4,463) and negative (at -4,463/-782) myocyte-selective regulatory elements. We showed that the basic and maximal S100B promoters were activated specifically by alpha(1)-adrenergic agonists through the alpha(1A)-adrenergic receptor, but not by any other trophic hormonal stimuli. The activation of the S100B promoter was mediated through the PKC signaling pathway. Transcription enhancer factor-1 (TEF-1) and related to TEF-1 (RTEF-1) influenced transcription from the maximal, but not the basic, promoter implicating active MCAT elements upstream from the basic promoter. Acting in opposing fashions, TEF-1 transrepressed the S100B promoter and RTEF-1 transactivated the promoter. Our results suggest that alpha(1)-adrenergic stimulation induces the S100B gene after myocardial infarction through the PKC signaling pathway and that this induction is modulated by TEF-1 and RTEF-1.
authors.affiliation: Division of Cardiology, Department of Medicine, The Toronto General Hospital Research Institute, University of Toronto, Ontario M5G 1L6, Canada.
authors.forename: James N
authors.initials: JN
authors.lastname: Tsoporis
authors.forename: Alexander
authors.initials: A
authors.lastname: Marks
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Van Eldik
authors.forename: David
authors.initials: D
authors.lastname: O'Hanlon
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Parker
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D027201:Cationic Amino Acid Transporter 1 / Q000378:metabolism; D027202:Cationic Amino Acid Transporter 2 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D032342:Muscle Cells / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000502:physiology; D009638:Norepinephrine / Q000097:blood; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012016:Reference Values; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection
chemical_list: D000316:Adrenergic alpha-Agonists; D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; D009414:Nerve Growth Factors; D009687:Nuclear Proteins; D018340:Receptors, Adrenergic, alpha-1; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; C579160:S100B protein, human; C579159:S100b protein, mouse; C579158:S100b protein, rat; C420826:Slc7a1 protein, mouse; D000091262:TEA Domain Transcription Factors; C057182:TEAD1 protein, human; C486309:TEAD4 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D011493:Protein Kinase C; D009638:Norepinephrine