Increase of glycogen storage by sodium arsenite in rat cortical astrocytes through glycogen synthase activation and its association to toxicity

Abstract

Objective: The present study aimed primarily to evaluate the effect of sodium arsenite exposure on glucose metabolism includes glycogen accumulation on rat cortical astrocytes. Furthermore, cell death analysis was concurrently done to determine the toxic effect of sodium arsenite on astrocytes. Methods: Rat cortical astrocytes derived from the cerebral cortices of neonatal Wistar rats were treated with sodium arsenite for 24 h. Glucose metabolism was evaluated by determining glucose uptake and glycogen accumulation using glucose uptake kit, and periodic acid–Schiff staining and transmission electron microscopy, respectively. Glycogen synthase (GS) and glycogen synthase kinase-3 (GSK3) were detected by Western blotting. The cell death analysis was assessed by propidium iodide staining. Results: Sodium arsenite exposure at 25 μM for 24 h significantly increased glucose uptake and glycogen content in rat cortical astrocytes. Sodium arsenite exposure significantly increased GS expression but decreased a ratio of GS phosphorylation at serine 641 (inactive) to GS, suggesting that there may be an increase in activity of GS. Moreover, sodium arsenite caused an increase in inactive serine phosphorylation of GSK3, a kinase that phosphorylates and inhibits GS. These results suggested that sodium arsenite increased glycogen synthesis through GS activation mediated by inhibition of GSK3. On the other hand, sodium arsenite exposure at 25 μM caused some degree of cellular damage and a slight increase in cell death in rat astrocytes. Conclusion: Sodium arsenite increased glycogen accumulation through GS activation and caused cell death in rat cortical astrocytes. These observations implicate that the enhancement of glycogen in rat astrocytes by sodium arsenite may be related to its toxicity. Hence, alteration of astrocyte glycogen metabolism may play a role in arsenic toxicity in the brain.