The biochemical mechanism of hypoxia-induced mobilization of glycogen in cultured cancer cell

Abstract

BACKGROUND: Metabolic reprogramming is one of the strategies adopted by cancer cells to survive hypoxic conditions. Recent findings suggest that hypoxic cancer cells derive the energy that they need through glycolysis using glucose mobilized from intracellular glycogen reserve. Glycogen phosphorylase (GP) is the major rate-determining enzyme for glycogen mobilization in many normal cells under the condition of starvation or physical exercise. The lysosomal alpha-glucosidase (GAA) has also been implicated in glycogen mobilization since deficiency of this enzyme is known to result in Glycogen Storage Disease Type II (Pompe disease). Although a role for GP in the mobilization of glycogen by cancer cells depleted of oxygen had been demonstrated, whether a similar role for GP (and GAA) could be demonstrated under deprivation of both glucose and oxygen is not yet known. This issue is addressed in this study by examining the intracellular level of glycogen in the absence and presence of pharmacological inhibitors of GP and/or …