Increased glucose concentration results in reduced proteasomal activity and the formation of glycogen positive aggresomal structures

Abstract

Recent studies indicate that glycogen, besides being a principal storage product, confers protection against cellular stress through an unknown physiological pathway. Abnormal glycogen inclusions have also been considered to underlie pathology in a few neurodegenerative disorders that are caused by proteolytic dysfunctions, although a link between proteolytic pathways and glycogen accumulation is yet to be established. In the present study, we investigated the subcellular localization of glycogen particles and report that their distribution is altered under physiological stress. Using a cellular model, we show that glycogen particles are recruited to the centrosomal aggresomal structures upon proteasomal or lysosomal blockade, and that this recruitment is dependent on the microtubule function. We also show that an increase in the glucose concentration leads to decreased cellular proteasomal activity and the formation of glycogen positive aggresomal structures. Proteasomal blockade also leads to the formation of diastase-resistant polyglucosan bodies. The glycogen particles in aggresomes might provide energy to the proteolytic process and/or function as a scaffold. Taken together, the findings of the present study suggest a functional link between proteasomal function and polyglucosan bodies, and also suggest that these two physiological processes could be linked in neurodegenerative disorders.