RRC ID 63839
Author Rascher M, Wittstein K, Winter B, Rupcic Z, Wolf-Asseburg A, Stadler M, Köster RW.
Title Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction.
Journal Biomolecules
Abstract Medicinal mushrooms of the genus Hericium are known to produce secondary metabolites with homeostatic properties for the central nervous system. We and others have recently demonstrated that among these metabolites cyathane diterpenoids and in particular erinacine C possess potent neurotrophin inducing properties in astrocytic cells. Yet, the signaling events downstream of erinacine C induced neurotrophin acitivity in neural-like adrenal phaeochromocytoma cells (PC12) cells have remained elusive. Similar, signaling events activated by erinacine C in astrocytic cells are unknown. Using a combination of genetic and pharmacological inhibitors we show that erinacine C induced neurotrophic activity mediates PC12 cell differentiation via the TrkA receptor and likely its associated PLCγ-, PI3K-, and MAPK/ERK pathways. Furthermore, a small library of transcriptional activation reporters revealed that erinacine C induces transcriptional activation mediated by DNA consensus binding sites of selected conserved transcription factor families. Among these, transcription is activated from an ETS consensus in a concentration dependent manner. Interestingly, induced ETS-consensus transcription occurs in parallel and independent of neurotrophin induction. This finding helps to explain the many pleiotropic functions of cyathane diterpenoids. Moreover, our studies provide genetic access to cyathane diterpenoid functions in astrocytic cells and help to mechanistically understand the action of cyathanes in glial cells.
Volume 10(10)
Published 2020-10-14
DOI 10.3390/biom10101440
PII biom10101440
PMID 33066380
PMC PMC7602259
MeSH Animals Astrocytes / drug effects* Astrocytes / physiology Binding Sites / genetics Cell Differentiation / drug effects Cell Differentiation / genetics Cells, Cultured Conserved Sequence / drug effects Conserved Sequence / genetics Diterpenes / pharmacology* ETS Motif Humans MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / genetics Nerve Growth Factor / genetics Nerve Growth Factor / metabolism PC12 Cells Protein Binding / drug effects Protein Binding / genetics Rats Transcription Factors / chemistry Transcription Factors / metabolism Transcriptional Activation / drug effects* Transcriptional Activation / genetics Up-Regulation / drug effects Up-Regulation / genetics
IF 4.082
Human and Animal Cells PC-12(RCB0009)