Regulation of the S100B gene by α1-adrenergic stimulation in cardiac myocytes

Abstract

We previously reported that S100B, a 20-kDa Ca2+-binding homodimer, inhibited the postinfarct myocardial hypertrophic response mediated by α1-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 α1-adrenergic agonists through the α1A-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 α1-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.