The effect of glycogen metabolism on the regulation of reactive oxidative species level in cultured cancer cells

Abstract

Glycogen is known to act as a fuel reserve in organs such as skeletal muscle and liver. Glycogen is also known to accumulate in many cancer cells suggesting a possible role for glycogen metabolism in cancers. Recently, studies using cancer cells that do not express glycogen phosphorylase showed that these cells had elevated level of reactive oxygen species (ROS). How inhibition of expression of glycogen phosphorylase may lead to increase in ROS level in tumour cells is not certain. It is hypothesised in this study that the accumulation of glycogen resulting from inhibition of its breakdown may lead to ROS production. Results of this study showed that inhibition of expression of glycogen synthase (GS) lead to almost 100% absence of glycogen and increase in intracellular ROS in the GS knockout cells. When compared to wild type cells, ROS level of cells lacking GS were higher irrespective of the absence or presence of glucose or glutamine. However, both wild type cells and GS knockout cells had similar levels of ROS in the absence of both glucose and glutamine. It is concluded that glycogen accumulation does not contribute to the increase of ROS due to inhibition of expression of glycogen synthase. Furthermore, the results of this study suggested that both wild type and GS knockout cells produce same amount of ROS through glucose and glycogen metabolism. Additional experiments demonstrated GS knockout cells exhibited increase expression of catalase, thioredoxin and Nrf2. Suggesting that the antioxidant mechanisms are involved in counteracting the increase in oxidative stress in GS knockout cells.