title: Activation of gene transcription via CIM0216, a synthetic ligand of transient receptor potential melastatin-3 (TRPM3) channels.
abstract: Several compounds have been proposed to stimulate TRPM3 Ca2+channels. We recently showed that stimulation of TRPM3 channels with pregnenolone sulfate activated the transcription factor AP-1, while other proposed TRPM3 ligands (nifedipine, D-erythro-sphingosine) exhibited either no or TRPM3-independent effects on gene transcription. Here, we have analyzed the transcriptional activity of CIM0216, a synthetic TRPM3 ligand proposed to have a higher potency and affinity for TRPM3 than pregnenolone sulfate. The results show that CIM0216 treatment of HEK293 cells expressing TRPM3 channels activated AP-1 and stimulated the transcriptional activation potential of c-Jun and c-Fos, 2 basic region leucine zipper transcription factors that constitute AP-1. CIM0216-induced gene transcription was attenuated by knock-down of TRPM3 or treatment with mefenamic acid, a TRPM3 inhibitor. CIM0216 was similarly or less capable in activating TRPM3-mediated gene transcription, suggesting that pregnenolone sulfate is still the ligand of choice for changing the gene expression pattern via TRPM3.
authors.affiliation: a Department of Medical Biochemistry and Molecular Biology , Saarland University Medical Faculty , Homburg , Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Rubil
authors.affiliation: a Department of Medical Biochemistry and Molecular Biology , Saarland University Medical Faculty , Homburg , Germany.
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
mesh_terms: D057809:HEK293 Cells; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D011284:Pregnenolone / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: C000623366:CIM0216; D006576:Heterocyclic Compounds, 4 or More Rings; D008024:Ligands; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D050053:TRPM Cation Channels; C475667:TRPM3 protein, human; D018808:Transcription Factor AP-1; C018370:pregnenolone sulfate; D011284:Pregnenolone
keywords: TRPM3; c-Fos; c-Jun; gene expression; lentivirus