Enhanced autophagic-lysosomal activity and increased BAG3-mediated selective macroautophagy as adaptive response of neuronal cells to chronic oxidative stress

Publication date: Available online 2 April 2019Source: Redox BiologyAuthor(s): Debapriya Chakraborty, Vanessa Felzen, Christof Hiebel, Elisabeth Stürner, Natarajan Perumal, Caroline Manicam, Elisabeth Sehn, Franz Grus, Uwe Wolfrum, Christian BehlAbstractOxidative stress and a disturbed cellular protein homeostasis (proteostasis) belong to the most important hallmarks of aging and of neurodegenerative disorders. The proteasomal and autophagic-lysosomal degradation pathways are key measures to maintain proteostasis. Here, we report that hippocampal cells selected for full adaptation and resistance to oxidative stress induced by hydrogen peroxide (oxidative stress-resistant cells, OxSR cells) showed a massive increase in the expression of components of the cellular autophagic-lysosomal network and a significantly higher overall autophagic activity. A comparative expression analysis revealed that distinct key regulators of autophagy are upregulated in OxSR cells. The observed adaptive autophagic response was found to be independent of the upstream autophagy regulator mTOR but is accompanied by a significant upregulation of further downstream components of the canonical autophagy network such as Beclin1, WIPI1 and the transmembrane ATG9 proteins. Interestingly, the expression of the HSP70 co-chaperone BAG3, mediator of BAG3-mediated selective macroautophagy and highly relevant for the clearance of aggregated proteins in cells, was found to be increased in OxSR cells that were con...

Source: Redox Biology - April 3, 2019 Category: Biology Source Type: research