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Increasing evidence suggests that trehalose, a non-reducing disaccharide, ameliorates disease phenotypes by activating autophagy in animal models of various human diseases, including neurodegenerative diseases. Multiple in vitro studies suggest that activation of transcription factor EB, a master regulator of lysosomal biogenesis and autophagy genes, is a major contributor to trehalose-induced autophagy at later stages of exposure. However, underlying causes of trehalose-induced autophagy possibly occur at the early stage of the exposure period. In this study, we investigated the effects of short-term exposure of HeLa cells to trehalose on several signal transduction pathways to elucidate the initial events involved in its beneficial effects. Phospho-protein array analysis revealed that trehalose decreases levels of phosphorylated c-Jun, a component of the transcription factor activator protein-1, after 6 h. Trehalose also rapidly reduced mRNA expression levels of c-Jun and JunB, a member of the Jun family, within 1 h, resulting in a subsequent decrease in their protein levels. Future studies, exploring the interplay between decreased c-Jun and JunB protein levels and beneficial effects of trehalose may provide novel insights into the mechanisms of trehalose action.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

PMID:35748379