Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction

Biomolecules

Zeljka Rupcic¹  Kathrin Wittstein¹  Marc Stadler¹  Barbara Winter²  Alexandra Wolf-Asseburg²  ReinhardW. Köster²  Monique Rascher² 

[1] Department Microbial Drugs, Helmholtz Centre for Infection Research GmbH and Institute of Microbiology, Technische Universität Braunschweig, Inhoffenstraße 7, 38124 Braunschweig, Germany;Division of Cellular and Molecular Biology, Zoological Institute, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany;

关键词: Hericium;    cyathane diterpenoid;    erinacine;    nerve growth factor;    brain derived neurotrophic factor;    neurotrophin;   

DOI  :  10.3390/biom10101440

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown