Erinacine C Activates Transcription from a Consensus ETS DNA Binding Site in Astrocytic Cells in Addition to NGF Induction.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Köster, Reinhard W
MetadataShow full item record
AbstractMedicinal 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.
CitationBiomolecules. 2020 Oct 14;10(10):1440. doi: 10.3390/biom10101440.
AffiliationHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International
- Erinacine A and related cyathane diterpenoids: Molecular diversity and mechanisms underlying their neuroprotection and anticancer activities.
- Authors: Bailly C, Gao JM
- Issue date: 2020 Sep
- Nerve growth factor- and epidermal growth factor-regulated gene transcription in PC12 pheochromocytoma and INS-1 insulinoma cells.
- Authors: Groot M, Boxer LM, Thiel G
- Issue date: 2000 Dec
- Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells.
- Authors: Cao CY, Zhang CC, Shi XW, Li D, Cao W, Yin X, Gao JM
- Issue date: 2018 Jul 18
- Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.
- Authors: Rupcic Z, Rascher M, Kanaki S, Köster RW, Stadler M, Wittstein K
- Issue date: 2018 Mar 6
- Three new cyathane diterpenes with neurotrophic activity from the liquid cultures of Hericium erinaceus.
- Authors: Zhang Y, Liu L, Bao L, Yang Y, Ma K, Liu H
- Issue date: 2018 Sep