High glucose leads to redistribution of the proteasomal system

The impact of high glucose on the cellular redox state, causing both induction of antioxidative systems and also enhanced protein oxidation is discussed for a long time. It is established that elevated glucose levels are disrupting the cellular proteostasis and influencing the proteasomal system. However, it is still unresolved whether this is due to a reaction of the cellular proteasomal system towards the high glucose or whether this is a secondary reaction to inflammatory stimuli. Therefore, we used a dermal fibroblast cell line exposed to high glucose in order to reveal whether a response of the proteasomal system takes place. We investigated the alpha 4 and the inducible i beta 5 subunits of the 20S proteasome, as well as the Rpn1-subunit of the 19S proteasomal regulator complex, measured activity of the 20S, 20S1, and 26S proteasome and detected as well changes in expression as a redistribution into the nucleus. Interestingly, while the activity of the proteasomal forms rather decreased under high glucose treatment; higher expression levels of components of the proteasomal system and higher concentrations of protein-bound 3-nitrotyrosine and Nrf2 (nuclear factor [erythroid-derived 2]-like 2) were detected. However, no change in the cytosol-nucleus distribution could be detected for most of the quantified parameters. We concluded that high glucose alone, without additional inflammatory stimuli, provokes a regulatory response on the ubiquitin-proteasomal system.

Automated summary

The impact of high glucose on cellular redox state, induction of antioxidative systems, and enhanced protein oxidation has been extensively discussed. It is known that elevated glucose levels disrupt cellular proteostasis and influence the proteasomal system. However, it is still unclear whether this is a direct reaction of the proteasomal system to high glucose or a secondary reaction to inflammatory stimuli. In this study, a dermal fibroblast cell line was exposed to high glucose to investigate if a response of the proteasomal system occurs. The study found changes in enzyme activity, expression levels, and nuclear redistribution of proteasomal components, suggesting that high glucose alone can provoke a regulatory response on the ubiquitin-proteasomal system without additional inflammatory stimuli.