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Front Mol Neurosci. 2018 Oct 22;11:386. doi: 10.3389/fnmol.2018.00386. eCollection 2018.

Trehalose Activates CRE-Dependent Transcriptional Signaling in HT22 Mouse Hippocampal Neuronal Cells: A Central Role for PKA Without cAMP Elevation.

Frontiers in molecular neuroscience

Erik Maronde

Affiliations

  1. Department of Medicine, Institute for Cellular and Molecular Anatomy, Goethe University, Frankfurt, Germany.

PMID: 30405349 PMCID: PMC6204353 DOI: 10.3389/fnmol.2018.00386

Abstract

Cyclic adenosine 3',5'monophosphate (cAMP) regulated element binding protein (CREB) is a transcription factor involved in many different signaling processes including memory storage and retrieval. The mouse hippocampal neuronal cell line HT22 is widely used as a model system for neuronal cell death and cellular signal pathway investigations. For the present work a variant of HT22 with a stably expressed CRE-luciferase (CRE-luc) reporter (HT22CRE) is introduced, characterized and used to investigate cAMP-dependent and independent CRE-dependent signal processes. Trehalose (Mykose or 1-α-Glucopyranosyl-1-α-glucopyranosid) is a naturally occurring disaccharide consisting of two α,α',1,1-glycosidic connected glucose molecules in a wide range of organisms but usually not found in mammals. Trehalose has been shown to activate autophagy, a process which regulates the degradation and recycling of proteins and organelles. The exact processes how trehalose application works on mammalian neuronal cells is not yet understood. The present work shows that trehalose application dose-dependently elevates CRE-luc activity in HT22 cells and acts synergistically with cAMP-elevating agents. In this pathway cAMP-dependent protein kinase (PKA) appears to be the most important factor and the stress kinase p38 and protein tyrosine kinases (PTKs) act as modulators.

Keywords: CRE-luciferase; hippocampal neuronal cell line; pCREB; signaling; trehalose

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